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Mansour RM, El-Sayyad GS, Abulsoud AI, Hemdan M, Faraag AHI, Ali MA, Elsakka EGE, Abdelmaksoud NM, Abdallah AK, Mahdy A, Ashraf A, Zaki MB, Elrebehy MA, Mohammed OA, Abdel-Reheim MA, Abdel Mageed SS, Alam Eldein KM, Doghish AS. The role of miRNAs in pathogenesis, diagnosis, and therapy of Helicobacter pylori infection, gastric cancer-causing bacteria: Special highlights on nanotechnology-based therapy. Microb Pathog 2025; 205:107646. [PMID: 40348207 DOI: 10.1016/j.micpath.2025.107646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/24/2025] [Accepted: 04/28/2025] [Indexed: 05/14/2025]
Abstract
Helicobacter pylori (H. pylori) infection and consequent inflammation in the stomach are widely recognized as major contributors to gastric cancer (GC) development. Recent investigations have placed considerable emphasis on uncovering the controlling influence of small RNA molecules known as microRNAs (miRNAs) in H. pylori-related diseases, particularly gastric cancer. This review aims to offer a comprehensive understanding of the intricate roles fulfilled by miRNAs in conditions associated with H. pylori infection. Exploring miRNA biogenesis pathways reveals their intimate connection with H. pylori infection, shedding light on the underlying molecular mechanisms driving disease progression and identifying potential intervention targets. An examination of epidemiological data surrounding H. pylori infection, including prevalence, risk factors, and transmission routes, underscores the imperative for preventive measures and targeted interventions. Incorporating insights from miRNA-related research into these strategies holds promise for enhancing their efficacy in controlling H. pylori spread. The symptoms, underlying mechanisms, and virulent characteristics of the bacteria highlight the intricate relationship between H. pylori and host cells, influencing the course of diseases. Within this complex web, miRNAs play pivotal roles, regulating various facets of H. pylori's development. MicroRNAs intricately involved in directing the immune response against H. pylori infection serve as key players in molding host defense mechanisms and impacting the bacterium's evasion tactics. Utilizing this knowledge holds the potential to drive forward groundbreaking therapeutic strategies. The diagnostic and prognostic capabilities of miRNAs in H. pylori infection highlight their effectiveness as non-invasive indicators for identifying diseases and evaluating risk. Integration of miRNA signatures into diagnostic algorithms holds promise for enhancing early detection and management of H. pylori-related diseases. MiRNA-based therapeutics offer a promising avenue for combatting H. pylori-induced gastric cancer, targeting specific molecular pathways implicated in tumorigenesis. H. pylori infection induces dysregulation of several miRNAs that contribute to antibiotic resistance, inflammation, and gastric cancer progression, including downregulation of tumor-suppressive miR-7 and miR-153 and upregulation of oncogenic miR-671-5p and miR-155-5p, which promote carcinogenesis and inflammation. Additionally, H. pylori manipulates host immune responses by upregulating miRNAs such as let-7f-5p, let-7i-5p, miR-146b-5p, and miR-185-5p that suppress HLA class II expression and antigen presentation, facilitating immune evasion and chronic gastritis that predispose to gastric cancer. Future research endeavors should focus on refining these therapeutic modalities and identifying novel targets to optimize clinical outcomes. By elucidating the multifaceted roles of miRNAs in H. pylori infection, this review provides invaluable insights into disease pathogenesis, diagnostics, and therapeutics, and the role of some nanoparticles in combating the H. pylori infection. Continued research efforts are imperative for translating these insights into clinical practice and addressing the global burden of H. pylori-related diseases.
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Affiliation(s)
- Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Gharieb S El-Sayyad
- Department of Medical Analysis Technology, Faculty of Applied Health Sciences Technology, Badr University in Cairo (BUC), Cairo, Egypt; Drug Microbiology Lab., Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Mohamed Hemdan
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed H I Faraag
- Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Medical Department, School of Biotechnology, Badr University in Cairo, Badr City, Cairo, 11829, Egypt.
| | - Mohamed A Ali
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
| | - Nourhan M Abdelmaksoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Asmaa K Abdallah
- Botany and Microbiology Department, Faculty of Science, Benha University, 13518 Benha, Egypt.
| | - Ahmed Mahdy
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Alaa Ashraf
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt; Department of Biochemistry, Faculty of Pharmacy, Menoufia National University, km Cairo-Alexandria Agricultural Road, Menofia, Egypt.
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Galala University, New Galala City, 43713, Suez, Egypt.
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
| | | | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Khaled M Alam Eldein
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed S Doghish
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
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Rai RP, Syed A, Elgorban AM, Abid I, Wong LS, Khan MS, Khatoon J, Prasad KN, Ghoshal UC. Expressions of selected microRNAs in gastric cancer patients and their association with Helicobacter pylori and its cag pathogenicity island. Microb Pathog 2025; 202:107442. [PMID: 40049249 DOI: 10.1016/j.micpath.2025.107442] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/12/2025]
Abstract
BACKGROUND Helicobacter pylori infection and the resulting inflammation of the stomach are widely recognized as the primary risk factors for the development of gastric cancer (human health). Despite numerous attempts, the correlation between various virulence factors of H. pylori and stomach cancer remains mainly unexplained. The cag pathogenicity island (cagPAI) is a widely recognized indicator of virulence in H. pylori. MicroRNAs play crucial roles in a wide range of biological and pathological processes and dysregulated expressions of miRNAs have been detected in numerous cancer types. However, research on the correlation between H. pylori infection and its cagPAI, as well as the differential expression of microRNAs in gastric cancer, is lacking. AIM The aim of this study was to examine the differential expression of miRNAs in 80 patients with gastric cancer, specifically in connection to the presence of H. pylori and its cag pathogenicity island (cagPAI). METHODS Biopsies of 80 gastric cancer patients were collected and used for H. pylori DNA isolation and tissue miRNA isolation, and further analyzed for cagPAI and miRNA expression and their association. RESULTS Elevated levels of miR-21, miR-155, and miR-223 were detected in malignant tissues. The expression of miR-21 and miR-223 was considerably elevated in biopsies that tested positive for H. pylori, whereas the expression of miR-34a was reduced. H. pylori cagPAI samples that are functionally intact exhibit greater expression of miR-21 and miR-223 compared to cagPAI samples that are partially deleted, in both normal and malignant tissues. CONCLUSION Thus, the novelty of our study lies in its focus on the differential expression of specific miRNAs in relation to the functional integrity of the cagPAI in H. pylori-infected gastric cancer patients, offering a more detailed understanding of the interplay between H. pylori virulence factors and miRNA regulation than previous studies.
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Affiliation(s)
- Ravi Prakash Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Asad Syed
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Abdallah M Elgorban
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Islem Abid
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia.
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Jahanarah Khatoon
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India.
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Alizadeh M, Ghasemi H, Bazhan D, Mohammadi Bolbanabad N, Rahdan F, Arianfar N, Vahedi F, Khatami SH, Taheri-Anganeh M, Aiiashi S, Armand N. MicroRNAs in disease States. Clin Chim Acta 2025; 569:120187. [PMID: 39938625 DOI: 10.1016/j.cca.2025.120187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/08/2025] [Accepted: 02/08/2025] [Indexed: 02/14/2025]
Abstract
This review highlights the role of miRNAs in various diseases affecting major organ systems. miRNAs are small, non-coding RNA molecules that regulate numerous genes. Dysregulation of miRNAs is linked to many pathological conditions due to their involvement in gene silencing and cellular pathways. We discuss miRNA expression patterns, their physiological and pathological roles, and how changes in miRNA levels contribute to disease. Notably, miRNAs like miR-499 and miR-21 are implicated in heart failure and atherosclerosis. miRNA dysregulation is also associated with colorectal and gastric cancers, influencing tumorigenesis and chemoresistance. In neurological diseases, miRNAs exhibit diverse profiles that affect neurodevelopment and degeneration. Additionally, miRNAs modulate cell function in reproductive organs, impacting fertility and cancer progression. miRNAs such as miR-192 and miR-204 serve as biomarkers for nephropathy and acute kidney injury. These miRNAs are involved in skeletal muscle diseases, contributing to conditions like osteoporosis and sarcopenia. miRNAs function as oncogenes or tumor suppressors in cancer, highlighting their potential in diagnostics and therapy. Further research is needed to develop miRNA-based diagnostics and treatments.
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Affiliation(s)
- Mehdi Alizadeh
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran
| | - Donya Bazhan
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Fereshteh Rahdan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Narges Arianfar
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzaneh Vahedi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
| | - Nezam Armand
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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Doghish AS, Elazazy O, Mohamed HH, Mansour RM, Ghanem A, Faraag AHI, Elballal MS, Elrebehy MA, Elesawy AE, Abdel Mageed SS, Saber S, Nassar YA, Abulsoud AI, Abdel-Reheim MA, Elawady AS, Ali MA, Basiouny MS, Hemdan M, Lutfy RH, Awad FA, El-Sayed SA, Ashour MM, El-Sayyad GS, Mohammed OA. A Review on miRNAs in Enteric Bacteria-mediated Host Pathophysiology: Mechanisms and Implications. J Biochem Mol Toxicol 2025; 39:e70160. [PMID: 39907181 DOI: 10.1002/jbt.70160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 12/22/2024] [Accepted: 01/16/2025] [Indexed: 02/06/2025]
Abstract
Recently, many studies focused on the billions of native bacteria found inside and all over the human body, commonly known as the microbiota, and its interactions with the eukaryotic host. One of the niches for such microbiota is the gastrointestinal tract (GIT), which harbors hundreds to thousands of bacterial species commonly known as enteric bacteria. Changes in the enteric bacterial populations were linked to various pathologies such as irritable bowel syndrome and obesity. The gut microbiome could affect the health status of individuals. MicroRNAs (miRNAs) are one of the extensively studied small-sized noncoding RNAs (ncRNAs) over the past decade to explore their multiple roles in health and disease. It was proven that miRNAs circulate in almost all body fluids and tissues, showing signature patterns of dysregulation associated with pathologies. Both cellular and circulating miRNAs participate in the posttranscriptional regulation of genes and are considered the potential key regulators of genes and participate in cellular communication. This manuscript explores the unique interplay between miRNAs and enteric bacteria in the gastrointestinal tract, emphasizing their dual role in shaping host-microbiota dynamics. It delves into the molecular mechanisms by which miRNAs influence bacterial colonization and host immune responses, linking these findings to gut-related diseases. The review highlights innovative therapeutic and diagnostic opportunities, offering insights for targeted treatments of dysbiosis-associated pathologies.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
| | - Ola Elazazy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Hend H Mohamed
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, Egypt
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Aml Ghanem
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Ahmed H I Faraag
- Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, Egypt
- Medical Department, School of Biotechnology, Badr University in Cairo, Badr City, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Galala University, New Galala City, Egypt
| | - Ahmed E Elesawy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Egypt
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
| | - Yara A Nassar
- Department of Botany, Faculty of Science, Biotechnology and Its Application Program, Mansoura University, Mansoura, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
- Department of Biochemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Egypt
| | | | - Alaa S Elawady
- Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Mohamed A Ali
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | | | - Mohamed Hemdan
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Radwa H Lutfy
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Farah A Awad
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Salma A El-Sayed
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Mohamed M Ashour
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Egypt
| | - Gharieb S El-Sayyad
- Medical Laboratory Technology Department, Faculty of Applied Health Sciences Technology, Badr University in Cairo (BUC), Cairo, Egypt
- Microbiology and Immunology Department, Faculty of Pharmacy, Galala University, New Galala city, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
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Srinivasan R, Ramadoss R, Kandasamy V, Ranganadin P, Green SR, Kasirajan A, Pillai AB. Exploring the regulatory role of small RNAs in modulating host-pathogen interactions: implications for bacterial and viral infections. Mol Biol Rep 2025; 52:115. [PMID: 39799541 DOI: 10.1007/s11033-024-10214-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 12/30/2024] [Indexed: 01/15/2025]
Abstract
MicroRNAs (miRNAs) and transfer RNA-derived stress-induced RNAs (tiRNAs) have emerged as crucial players in the post-transcriptional regulation of gene expression in various cellular processes, including immunity and host defense against infections. In recent years, increasing evidence has highlighted their complex role in influencing the host response during viral and bacterial infections. miRNAs have been shown to play multiple roles in host-pathogen interaction like TLR activation and altered disease virulence during bacterial infections. In the context of viral infections, miRNAs are involved in regulating viral replication, pathogenesis, and immune evasion. Similarly, tiRNAs have recently emerged as novel players in bacterial and viral infections such as modulating bacterial growth, adaptation to stress conditions, host antiviral responses, and impacting viral replication and pathogenesis. This review provides a comprehensive analysis of the potential of miRNA expression profiles as diagnostic biomarkers to differentiate between bacterial and viral infections. Further discusses the key pathways through which small RNAs regulate bacterial and viral infection-related diseases.
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Affiliation(s)
- Rajesh Srinivasan
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Ramya Ramadoss
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Vanathy Kandasamy
- Department of Microbiology, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Pajanivel Ranganadin
- Department of Pulmonary Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Siva Ranganathan Green
- Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Anand Kasirajan
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India
| | - Agieshkumar Balakrishna Pillai
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607402, India.
- Institute of Advanced Virology, Trivandrum, Kerala, 695 317, India.
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Chen S, Lei Z, Sun T. The critical role of miRNA in bacterial zoonosis. Int Immunopharmacol 2024; 143:113267. [PMID: 39374566 DOI: 10.1016/j.intimp.2024.113267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 08/21/2024] [Accepted: 09/24/2024] [Indexed: 10/09/2024]
Abstract
The public's health and the financial sustainability of international societies remain threatened by bacterial zoonoses, with limited reliable diagnostic and therapeutic options available for bacterial diseases. Bacterial infections influence mammalian miRNA expression in host-pathogen interactions. In order to counteract bacterial infections, miRNAs participate in gene-specific expression and play important regulatory roles that rely on translational inhibition and target gene degradation by binding to the 3' non-coding region of target genes. Intriguingly, according to current studies, that exogenous miRNAs derived from plants could potentially serve as effective medicinal components sourced from traditional Chinese medicine plants. These exogenous miRNAs exhibit stable functionality in mammals and mimic the regulatory roles of endogenous miRNAs, illuminating the molecular processes behind the therapeutic effects of plants. This review details the immune defense mechanisms of inflammation, apoptosis, autophagy and cell cycle disturbance caused by some typical bacterial infections, summarizes the role of some mammalian miRNAs in regulating these mechanisms, and introduces the cGAS-STING signaling pathway in detail. Evidence suggests that this newly discovered immune defense mechanism in mammalian cells can also be affected by miRNAs. Meanwhile, some examples of transboundary regulation of mammalian mRNA and even bacterial diseases by exogenous miRNAs from plants are also summarized. This viewpoint provides fresh understanding of microbial tactics and host mechanisms in the management of bacterial illnesses.
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Affiliation(s)
- Si Chen
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China
| | - Zhixin Lei
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
| | - Taolei Sun
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
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7
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Jahantab MB, Salehi M, Koushki M, Farrokhi Yekta R, Amiri-Dashatan N, Rezaei-Tavirani M. Modelling of miRNA-mRNA Network to Identify Gene Signatures with Diagnostic and Prognostic Value in Gastric Cancer: Evidence from In-Silico and In-Vitro Studies. Rep Biochem Mol Biol 2024; 13:281-300. [PMID: 39995653 PMCID: PMC11847593 DOI: 10.61186/rbmb.13.2.281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 12/08/2024] [Indexed: 02/26/2025]
Abstract
Background Gastric cancer (GC) is a prevalent malignancy with high recurrence. Advances in systems biology have identified molecular pathways and biomarkers. This study focuses on discovering gene and miRNA biomarkers for diagnosing and predicting survival in GC patients. Methods Three sets of genes (GSE19826, GSE81948, and GSE112369) and two sets of miRNA expression (GSE26595, GSE78775) were obtained from the Gene Expression Omnibus (GEO), and subsequently, differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Functional pathway enrichment, DEG-miR-TF-protein-protein interaction network, DEM-mRNA network, ROC curve, and survival analyses were performed. Finally, qRT-PCR was applied to validate our results. Results From the high-throughput profiling studies of GC, we investigated 10 candidate mRNA and 7 candidate miRNAs as potential biomarkers. Expression analysis of these hubs revealed that 5 miRNAs (including miR-141-3p, miR-204-5p, miR-338-3p, miR-609, and miR-369-5p) were significantly upregulated compared to the controls. The genes with the highest degree included 6 upregulated and 4 downregulated genes in tumor samples compared to controls. The expression of miR-141-3p, miR-204-5p, SESTD1, and ANTXR1 were verified in vitro from these hub DEMs and DEGs. The findings indicated a decrease in the expression of miR-141-3p and miR-204-5p and increased expression of SESTD1 and ANTXR1 in GC cell lines compared to the GES-1 cell line. Conclusions The current investigation successfully recognized a set of prospective miRNAs and genes that may serve as potential biomarkers for GC's early diagnosis and prognosis.
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Affiliation(s)
- Mohammad Bagher Jahantab
- Clinical Research Development Unit, Shahid Jalil Hospital, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Mohammad Salehi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Mehdi Koushki
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Reyhaneh Farrokhi Yekta
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nasrin Amiri-Dashatan
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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8
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Xu H, Huang K, Shi M, Gong H, Han M, Tian W, Wang X, Zhang D. MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application. Pharmacol Res 2024; 205:107216. [PMID: 38761883 DOI: 10.1016/j.phrs.2024.107216] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/20/2024]
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Ke Huang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Mingxuan Shi
- Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Hang Gong
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Mengyu Han
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Wenji Tian
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Xiaoying Wang
- Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
| | - Dekui Zhang
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
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9
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Rezaeepoor M, Keramat F, Jourghasemi S, Rahmanpour M, Lipsa A, Hajilooi M, Solgi G. MicroRNA -21 expression as an auxiliary diagnostic biomarker of acute brucellosis. Mol Biol Rep 2024; 51:264. [PMID: 38302783 DOI: 10.1007/s11033-023-09193-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 12/21/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND This study aimed to measure the expression levels of peripheral blood miRNAs in brucellosis and their involvement in the different phases of the brucellosis. METHODS The expression levels of miRNAs including miR-210, miR-155, miR-150, miR-146a, miR-139-3p, miR-125a-5p, miR-29 and miR-21 were quantified in 57 brucellosis patients subgrouped into acute, under treatment & relapse phase and 30 healthy controls (HCs) using real-time polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) analysis curve analysis was performed to find a biomarker for discrimination of different phases of brucellosis. RESULTS The expression of miR-155, miR-146a, miR-125a-5p, miR-29, and miR-21 was found to be elevated in the acute brucellosis patients compared to HCs. miR-29 changed in under-treatment patients, while miR-139-3p and miR-125a-5p showed alterations in relapse cases. The ROC curve analysis depicted the potential involvement of miR-21 in the pathogenesis of acute brucellosis. CONCLUSION The expression level of miR-21 is significantly augmented in acute brucellosis and has the potential to be a contributing diagnostic factor for acute infection.
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Affiliation(s)
- Mahsa Rezaeepoor
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran
| | - Fariba Keramat
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran
- Department of Infectious Diseases, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sanaz Jourghasemi
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran
| | - Mina Rahmanpour
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran
| | - Anuja Lipsa
- Cancer Genetic Laboratory, Advanced Centre for Treatment Research and Education in Cancer-Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India
| | - Mehrdad Hajilooi
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran.
| | - Ghasem Solgi
- Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Shariati Ave, Opposite to Lona Park, P.O. Box: 6517838736, Hamadan, Iran.
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10
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Liao TL, Chen IC, Chen HW, Tang KT, Huang WN, Chen YH, Chen YM. Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C. Sci Rep 2024; 14:937. [PMID: 38195767 PMCID: PMC10776842 DOI: 10.1038/s41598-023-50963-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 12/28/2023] [Indexed: 01/11/2024] Open
Abstract
Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.
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Affiliation(s)
- Tsai-Ling Liao
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Rong-Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan
| | - I-Chieh Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Hong-Wei Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kuo-Tung Tang
- Rong-Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan
- School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Nan Huang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan
- School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Hsing Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan
- School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Ming Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
- Rong-Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan.
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan.
- School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
- Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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11
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Chekhonatsky VA, Mirzaev KB, Pavlova GV, Usachev DY, Zakharova NB, Chekhonatsky AA, Kuznetsov AV, Gorozhanin AV, Dreval ON. [Genetic factors in degenerative disc disease]. ZHURNAL VOPROSY NEIROKHIRURGII IMENI N. N. BURDENKO 2024; 88:112-118. [PMID: 38549418 DOI: 10.17116/neiro202488021112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
OBJECTIVE To analyze available literature data on the role of genetic factors in degenerative disc disease. METHODOLOGY We reviewed the PubMed, MEDLINE, Cohrane Library, e-Library databases using the following keywords: degenerative spine lesions, intervertebral disc herniation, pathogenesis, genetic regulation. RESULTS Searching depth was 2002-2022. We reviewed 84 references. Exclusion criteria: duplicate publications, reviews without detailed description of results, opinions. Finally, we included 43 the most significant studies. CONCLUSION There are literature data on proinflammatory cytokines, growth factors and osteodestructive processes in pathogenesis of degenerative disc disease. However, there is only fragmentary information about the role of genetic regulation of these processes. Some factors, such as microRNA, TGF-b, VEGF, MMP are still poorly understood.
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Affiliation(s)
- V A Chekhonatsky
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
| | - K B Mirzaev
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
| | - G V Pavlova
- Burdenko Neurosurgical Center, Moscow, Russia
- Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Moscow, Russia
| | - D Yu Usachev
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
- Burdenko Neurosurgical Center, Moscow, Russia
| | - N B Zakharova
- Razumovsky Saratov State Medical University, Saratov, Russia
| | | | - A V Kuznetsov
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
| | - A V Gorozhanin
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
- Botkin Moscow City Clinical Hospital, Moscow, Russia
| | - O N Dreval
- Russian Medical Academy of Continuous Postgraduate Education, Moscow, Russia
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12
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Liu H, Tan S, Chen Y, Chen X, Liu X, Li Z, Wang N, Han S, Wu Z, Ma J, Shi K, Wang W, Sha Z. Regulatory mechanism of miR-722 on C5aR1 and its functions against bacterial inflammation in half-smooth tongue sole (Cynoglossus semilaevis). Int J Biol Macromol 2023; 252:126445. [PMID: 37611685 DOI: 10.1016/j.ijbiomac.2023.126445] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 08/25/2023]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs involved in various biological processes, including immunity. Previously, we investigated the miRNAs of half-smooth tongue sole (Cynoglossus semilaevis) and found that miR-722 (designated Cse-miR-722) was significantly differentially expressed after infection with Vibrio anguillarum, reflecting its importance in immune response. Our preliminary bioinformatic analysis suggested that Cse-miR-722 could target C5aR1 (designated CsC5aR1), which was known to play crucial roles in complement activation and inflammatory response, as a receptor of C5a. However, the underlying mechanisms of their interactions and specific functions in inflammatory and immune response are still enigmas. In this study, we successfully cloned the precursor sequence of Cse-miR-722 (94 bp) and the full length of CsC5aR1 (1541 bp, protein molecular weight 39 kDa). The target gene of Cse-miR-722 was verified as CsC5aR1 by a dual luciferase reporter assay, and Cse-miR-722 was confirmed to regulate CsC5aR1 at the protein level using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The expression of CsC5aR1 and Cse-miR-722 in liver cells and four immune tissues of half-smooth tongue sole changed significantly after LPS stimulation and infection with V. anguillarum. To explore the functional role of Cse-miR-722 in half-smooth tongue sole, we performed both in vitro and in vivo experiments. Cse-miR-722 was observed to affect phagocytosis and respiratory burst activity of macrophages by regulating CsC5aR1 in half-smooth tongue sole. Furthermore, we found that Cse-miR-722 regulated the expression of CsC5aR1, CsC5a, and the inflammatory factors CsIL1-β, CsIL6, CsIL8, and CsTNF-α both in vitro and in vivo. In addition, Cse-miR-722 reduced mortality and pathological damage. This study clarified the regulatory mechanism of Cse-miR-722 on CsC5aR1 and provided insight into the regulatory roles of Cse-miR-722 in immune responses, laying a theoretical foundation for the feasibility of using miR-722 to prevent and control bacterial diseases in teleost.
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Affiliation(s)
- Hongning Liu
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Suxu Tan
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Yadong Chen
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Xuejie Chen
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Xinbao Liu
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Zhujun Li
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Ningning Wang
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China; College of Basic Medicine, Qingdao University, Qingdao 266071, China
| | - Sen Han
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Zhendong Wu
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Jie Ma
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Kunpeng Shi
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Wenwen Wang
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Zhenxia Sha
- Institute of Aquatic Biotechnology, College of Life Sciences, Qingdao University, Qingdao 266071, China.
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13
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Iyer K, Erkert L, Becker C. Know your neighbors: microbial recognition at the intestinal barrier and its implications for gut homeostasis and inflammatory bowel disease. Front Cell Dev Biol 2023; 11:1228283. [PMID: 37519301 PMCID: PMC10375050 DOI: 10.3389/fcell.2023.1228283] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/07/2023] [Indexed: 08/01/2023] Open
Abstract
Intestinal epithelial cells (IECs) perform several physiological and metabolic functions at the epithelial barrier. IECs also play an important role in defining the overall immune functions at the mucosal region. Pattern recognition receptors (PRRs) on the cell surface and in other cellular compartments enable them to sense the presence of microbes and microbial products in the intestinal lumen. IECs are thus at the crossroads of mediating a bidirectional interaction between the microbial population and the immune cells present at the intestinal mucosa. This communication between the microbial population, the IECs and the underlying immune cells has a profound impact on the overall health of the host. In this review, we focus on the various PRRs present in different cellular compartments of IECs and discuss the recent developments in the understanding of their role in microbial recognition. Microbial recognition and signaling at the epithelial barrier have implications in the maintenance of intestinal homeostasis, epithelial barrier function, maintenance of commensals, and the overall tolerogenic function of PRRs in the gut mucosa. We also highlight the role of an aberrant microbial sensing at the epithelial barrier in the pathogenesis of inflammatory bowel disease (IBD) and the development of colorectal cancer.
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Affiliation(s)
- Krishna Iyer
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, United States
| | - Lena Erkert
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Christoph Becker
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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14
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Zhang J, Tian W, Wang F, Liu J, Huang J, Duangmano S, Liu H, Liu M, Zhang Z, Jiang X. Advancements in understanding the role of microRnas in regulating macrophage polarization during acute lung injury. Cell Cycle 2023; 22:1694-1712. [PMID: 37415386 PMCID: PMC10446815 DOI: 10.1080/15384101.2023.2230018] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/11/2023] [Accepted: 06/04/2023] [Indexed: 07/08/2023] Open
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical and life-threatening illness that causes severe dyspnea, and respiratory distress and is often caused by a variety of direct or indirect factors that damage the alveolar epithelium and capillary endothelial cells, leading to inflammation factors and macrophage infiltration. Macrophages play a crucial role in the progression of ALI/ARDS, exhibiting different polarized forms at different stages of the disease that control the disease outcome. MicroRNAs (miRNA) are conserved, endogenous, short non-coding RNAs composed of 18-25 nucleotides that serve as potential markers for many diseases and are involved in various biological processes, including cell proliferation, apoptosis, and differentiation. In this review, we provide a brief overview of miRNA expression in ALI/ARDS and summarize recent research on the mechanism and pathways by which miRNAs respond to macrophage polarization, inflammation, and apoptosis. The characteristics of each pathway are also summarized to provide a comprehensive understanding of the role of miRNAs in regulating macrophage polarization during ALI/ARDS.
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Affiliation(s)
- Jianhua Zhang
- Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wanyi Tian
- Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Fang Wang
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jiao Liu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jiang Huang
- Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Suwit Duangmano
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Hao Liu
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Minghua Liu
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhuo Zhang
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xian Jiang
- Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Department of Anesthesiology, Luzhou People’s Hospital, Luzhou, China
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15
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Debbarma A, Mansolf M, Khatri VA, Valentino JA, Sapi E. Effect of Borrelia burgdorferi on the Expression of miRNAs in Breast Cancer and Normal Mammary Epithelial Cells. Microorganisms 2023; 11:1475. [PMID: 37374977 DOI: 10.3390/microorganisms11061475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 05/28/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
Breast cancer is one of the leading causes of death in women worldwide. Recent studies have demonstrated that inflammation due to infections with microorganisms could play a role in breast cancer development. One of the known human pathogens, Borrelia burgdorferi, the causative agent of Lyme disease, has been shown to be present in various types of breast cancer and is associated with poor prognosis. We reported that B. burgdorferi can invade breast cancer cells and affect their tumorigenic phenotype. To better understand the genome-wide genetic changes caused by B. burgdorferi, we evaluated the microRNA (miRNA or miR) expression profiles of two triple-negative breast cancer cell lines and one non-tumorigenic mammary cell line before and after B. burgdorferi infection. Using a cancer-specific miRNA panel, four miRNAs (miR-206, 214-3p, 16-5p, and 20b-5p) were identified as potential markers for Borrelia-induced changes, and the results were confirmed by quantitative real-time reverse transcription (qRT-PCR). Among those miRNAs, miR-206 and 214 were the most significantly upregulated miRNAs. The cellular impact of miR-206 and 214 was evaluated using DIANA software to identify related molecular pathways and genes. Analyses showed that the cell cycle, checkpoints, DNA damage-repair, proto-oncogenes, and cancer-related signaling pathways are mostly affected by B. burgdorferi infection. Based on this information, we have identified potential miRNAs which could be further evaluated as biomarkers for tumorigenesis caused by pathogens in breast cancer cells.
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Affiliation(s)
- Ananya Debbarma
- Lyme Disease Research Group, Department of Biology and Environmental Science, University of New Haven, 300 Boston Post Road, West Haven, CT 06516, USA
| | - Miranda Mansolf
- Lyme Disease Research Group, Department of Biology and Environmental Science, University of New Haven, 300 Boston Post Road, West Haven, CT 06516, USA
| | - Vishwa A Khatri
- Lyme Disease Research Group, Department of Biology and Environmental Science, University of New Haven, 300 Boston Post Road, West Haven, CT 06516, USA
| | - Justine A Valentino
- Lyme Disease Research Group, Department of Biology and Environmental Science, University of New Haven, 300 Boston Post Road, West Haven, CT 06516, USA
| | - Eva Sapi
- Lyme Disease Research Group, Department of Biology and Environmental Science, University of New Haven, 300 Boston Post Road, West Haven, CT 06516, USA
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Tong T, Zhou Y, Huang Q, Xiao C, Bai Q, Deng B, Chen L. The regulation roles of miRNAs in Helicobacter pylori infection. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023:10.1007/s12094-023-03094-9. [PMID: 36781601 DOI: 10.1007/s12094-023-03094-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/17/2023] [Indexed: 02/15/2023]
Abstract
Helicobacter pylori is a kind of Gram-negative bacteria that parasitizes on human gastric mucosa. Helicobacter pylori infection is very common in human beings, which often causes gastrointestinal diseases, including chronic gastritis, duodenal ulcer and gastric cancer. MicroRNAs are a group of endogenous non-coding single stranded RNAs, which play an important role in cell proliferation, differentiation, autophagy, apoptosis and inflammation. In recent years, relevant studies have found that the expression of microRNA is changed after Helicobacter pylori infection, and then regulate the biological process of host cells. This paper reviews the regulation role of microRNAs on cell biological behavior through different signal pathways after Helicobacter pylori infection.
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Affiliation(s)
- Ting Tong
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - You Zhou
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qiaoling Huang
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Cui Xiao
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qinqin Bai
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Bo Deng
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Lili Chen
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China.
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17
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Allahverdy J, Rashidi N. MicroRNAs induced by Listeria monocytogenes and their role in cells. Microb Pathog 2023; 175:105997. [PMID: 36669673 DOI: 10.1016/j.micpath.2023.105997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 01/16/2023] [Accepted: 01/16/2023] [Indexed: 01/19/2023]
Abstract
Listeria monocytogenes (Lm) causes abortions at high rates and threatens newborns' lives. Also, the elderly and immunocompromised individuals are particularly vulnerable neurologically. The bacterium exerts its pathogenesis intracellularly by manipulating cell organs. It manipulates nucleus elements, microRNAs (miRNAs), in order to increase survival and evade immunity. miRNAs are small non-coding RNAs that degrade gene expression post-transcriptionally. Any alteration to the expression of miRNAs affects various cascades in cells, especially immunity-related responses. Thus, utilizing miRNAs as a novel therapeutic agent not only restricts infection but enhances immunity reactions. This review provides an overview of miRNAs in listeriosis, their role in cells, and their prospects as therapy.
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Affiliation(s)
- Javad Allahverdy
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Niloufar Rashidi
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Liu Y, Song J, Gu J, Xu S, Wang X, Liu Y. The Role of BTBD7 in Normal Development and Tumor Progression. Technol Cancer Res Treat 2023; 22:15330338231167732. [PMID: 37050886 PMCID: PMC10102955 DOI: 10.1177/15330338231167732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023] Open
Abstract
BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.
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Affiliation(s)
- Yun Liu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Jiwu Song
- Weifang People's Hospital, First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Jianchang Gu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Shuangshuang Xu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Xiaolan Wang
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Yunxia Liu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
- Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
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Oana SM, Claudia B, Lelia RA, Simona M, Claudia C, Daniela DE. Differential Expression of Tissular miRNA-155 in Pediatric Gastritis. J Clin Med 2022; 11:3351. [PMID: 35743416 PMCID: PMC9224896 DOI: 10.3390/jcm11123351] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/01/2022] [Accepted: 06/09/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND MicroRNA molecules, among them the intensely studied miRNA-155 (miR-155), are regarded as potential biomarkers of chronic gastric inflammation and premalignant lesion progression. However, literature data are scarce in terms of pediatric studies and in the evaluation of the predictive role of miRNA in early gastric inflammation. This study aims to assess the differential expression of miR-155 in relation to pediatric gastritis. METHODS The present research was conducted on 192 patients with chronic dyspeptic symptoms who underwent upper digestive endoscopy. Bioptic samples were harvested for histopathological analysis and tissue miR-155 depiction. MiR-155 expression analysis was carried out through quantitative real-time polymerase chain reaction (qRT-PCR). The study population was divided into two groups: controls (93 patients) and study group (99 patients) with inflammatory modifications. RESULTS MiR-155 expression was augmented in patients with gastritis but did not differ significantly from controls (p = 0.16). An increase in miR-155 expression was noted in relation to chronic gastritis, H. pylori infection, or increase in gastritis severity, but these variations were not important (p = 0.30, p = 0.44, and p = 0.45, respectively). CONCLUSIONS According to our study, pediatric gastritis increases, but does not greatly influence, miR-155 expression. Dynamic evaluation of miR-155 might enlighten its prognostic role in pediatric gastritis.
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Affiliation(s)
- Săsăran Maria Oana
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Bănescu Claudia
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Riza Anca Lelia
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, Petru Rareș Street No 2, 200349 Craiova, Romania;
| | - Mocan Simona
- Pathology Department, County Emergency Clinical Hospital of Targu Mures, Gheorghe Marinescu Street No 50, 540136 Targu Mures, Romania;
| | - Cârstea Claudia
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Dobru Ecaterina Daniela
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
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20
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MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis. Dig Dis Sci 2022; 67:2209-2219. [PMID: 34341909 DOI: 10.1007/s10620-021-07022-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 04/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1β, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.
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21
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Helicobacter pylori Infection Mediates Inflammation and Tumorigenesis-Associated Genes Through miR-155-5p: An Integrative Omics and Bioinformatics-Based Investigation. Curr Microbiol 2022; 79:192. [PMID: 35551487 DOI: 10.1007/s00284-022-02880-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 04/15/2022] [Indexed: 11/03/2022]
Abstract
Helicobacter pylori (H. pylori) is a major human pathogenic bacterium that survives in the gastric mucosa. The aim of this study is to evaluate the expression of the target gene network of miR-155-5p in H. pylori-related gastritis using a combination of public gene expression datasets and web-based platforms. To evaluate the expression of genes related to gastritis, we used two datasets from Gene Expression Omnibus (GEO) database. Then, we determined the overlaps between the predicted miR-155-5p target genes and gastritis-dysregulated GEO datasets genes; in the next step, we identified the possible miR-155-5p target-DEGs (Target-Differentially Expressed Genes). Also, we performed multiple bioinformatics analyses to identify the most important targets and downstream pathways associated with this miRNA. Using the UCSC cancer genomic browser analysis tool, we investigated the expression of hub genes in relation to gastric cancer and H. pylori infection, as well as the potential role of hub genes in gastritis, inflammation, and cancer. In this regard, 28 differentially expressed target genes of miR-155-5p were identified. Most of the captured target genes were correlated with the host immune response and inflammation. Based on the specific patterns of expression in gastritis and cancer, CD9, MST1R, and ADAM10 were candidates for the most probable targets of miR-155-5p. Although the focus of this study is primarily on bioinformatics, we think that our findings should be experimentally validated before they can be used as potential therapeutic and diagnostic tools.
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22
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Modulation of Mismatch Repair and the SOCS1/p53 Axis by microRNA-155 in the Colon of Patients with Primary Sclerosing Cholangitis. Int J Mol Sci 2022; 23:ijms23094905. [PMID: 35563301 PMCID: PMC9100906 DOI: 10.3390/ijms23094905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 04/24/2022] [Accepted: 04/26/2022] [Indexed: 12/10/2022] Open
Abstract
Deficient mismatch repair (MMR) proteins may lead to DNA damage and microsatellite instability. Primary sclerosing cholangitis (PSC) is a risk factor for colitis-associated colon cancer. MiR-155 is suggested to act as a key regulating node, linking inflammation and tumorigenesis. However, its involvement in the chronic colitis of PSC-UC patients has not been examined. We investigated the involvement of miR-155 in the dysregulation of MMR genes and colitis in PSC patients. Colon tissue biopsies were obtained from patients with PSC, PSC with concomitant ulcerative colitis (PSC-UC), uncomplicated UC, and healthy controls (n = 10 per group). In the ascending colon of PSC and PSC-UC patients, upregulated miR-155 promoted high microsatellite instability and induced signal transducer and activator of transcription 3 (STAT-3) expression via the inhibition of suppressors of cytokine signalling 1 (SOCS1). In contrast, the absence of miR-155 overexpression in the sigmoid colon of PSC-UC patients activated the Il-6/S1PR1 signalling pathway and imbalanced the IL17/FOXP3 ratio, which reinforces chronic colitis. Functional studies on human intestinal epithelial cells (HT-29 and NCM460D) confirmed the role of miR-155 over-expression in the inhibition of MMR genes and the modulation of p53. Moreover, those cells produced more TNFα upon a lipopolysaccharide challenge, which led to the suppression of miR-155. Additionally, exposure to bile acids induced upregulation of miR-155 in Caco-2 cell lines. Thus, under different conditions, miR-155 is involved in either neoplastic transformation in the ascending colon or chronic colitis in the sigmoid colon of patients with PSC. New insight into local modulation of microRNAs, that may alter the course of the disease, could be used for further research on potential therapeutic applications.
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23
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Zhang X, Chen J, Cheng H, Zhu J, Dong Q, Zhang H, Chen Z. MicroRNA-155 expression with Brucella infection in vitro and in vivo and decreased serum levels of MicroRNA-155 in patients with brucellosis. Sci Rep 2022; 12:4181. [PMID: 35264708 PMCID: PMC8907217 DOI: 10.1038/s41598-022-08180-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 03/03/2022] [Indexed: 11/09/2022] Open
Abstract
Infection with Brucella is characterized by the inhibition of host immune responses. MicroRNA-155 (miR-155) has been implicated in the immune response to many diseases. In this study, its expression during Brucella 16M infection of macrophages and mice was analyzed. Expression of miR-155 was significantly induced in macrophages at 24 h post infection. Further, an analysis of infected mice showed that miR-155 was inhibited at 7 and 14 days but induced at 28 days. Interestingly, this trend in induction or inhibition was reversed at 7 and 14 days in 16M△virB-infected mice. This suggested that decreased expression of miR-155 at an early stage of infection was dependent on intracellular replication. In humans with brucellosis, serum levels of miR-155 were significantly decreased compared to those in individuals without brucellosis and healthy volunteers. Significant correlations were observed between serum level of miR-155 and serum anti-Brucella antibody titers and the sweating symptom. This effect suggests that Brucella interferes with miR-155-regulated immune responses via a unique mechanism. Taken together, data from this study indicate that Brucella infection affects miR-155 expression and that human brucellosis patients show decreased serum levels of miR-155.
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Affiliation(s)
- Xi Zhang
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China
| | - Jingjing Chen
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China
| | - Huimin Cheng
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China.,Animal Husbandry and Veterinary Research Institute, Beijing Academy of Agriculture and Forestry Sciences, Beijing, People's Republic of China
| | - Jinying Zhu
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China
| | - Qiao Dong
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China
| | - Huan Zhang
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China.
| | - Zeliang Chen
- Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Liaoning Province, Shenyang, 110866, People's Republic of China.
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Assessment of Association between miR-146a Polymorphisms and Expression of miR-146a, TRAF-6, and IRAK-1 Genes in Patients with Brucellosis. Mol Biol Rep 2022; 49:1995-2002. [PMID: 34981334 DOI: 10.1007/s11033-021-07014-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 11/24/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Brucellosis is a major zoonosis all over the world. MicroRNAs are significant gene expression regulators and could be involved during the infections and also genetic alterations in the miRNAs sequence can affect primary miRNAs and precursor miRNAs processing and thus alter miRNAs expression. Current research studied the impact of the miR-146a polymorphism on miR-146a, TRAF-6, and IRAK-1 genes expression in patients with brucellosis illness. METHODS AND RESULTS In this research, 25 patients with brucellosis and 25 healthy participants with determined genotypes for miR-SNP rs2910164 and miR-SNP rs57095329 were recruited. IRAK-1, TRAF-6, and miR-146a expressions in peripheral blood mononuclear cells (PBMCs) were specified by quantitative real- time PCR (qRT-PCR). Moreover, interleukin-1β (IL-1β) and tumor necrosis factor- alpha (TNF-α) serum levels were assessed by a sandwich enzyme-linked immunosorbent assay (ELISA) technique. There was no significant difference in the expression level of miR-146a, IRAK-1, and TRAF-6, among the patients with brucellosis and control group. TRAF-6 PBMCs expression levels in the distinctive genotypes of rs2910164 were significantly observed in patients (P = 0.048). No significant distinctions were found in miR-146a, IRAK-1, and TRAF-6 expression levels and among the rs57095329 different genotypes in brucellosis patients and controls. Meanwhile, no significant relationship was found between the rs2910164 and rs57095329 genotypes and the serum level of cytokines mentioned between the two groups. We did not find any association between expression of TRAF-6, miR-146a, and IRAK-1 in PBMCs, and cytokines serum levels with two single nucleotide polymorphisms (SNPs) in miR-146a. CONCLUSIONS To the best of writers' knowledge, this research is the first one evaluating the probable link between the miR-146a rs2910164 and rs57095329 variant with miRNAs, relevant cytokine levels, and target genes in brucellosis.
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25
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Liu AR, Yan ZW, Jiang LY, Lv Z, Li YK, Wang BG. The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response. Front Med (Lausanne) 2022; 9:1009021. [PMID: 36314013 PMCID: PMC9606473 DOI: 10.3389/fmed.2022.1009021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 09/20/2022] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the globally recognized causative factors of gastric cancer (GC). Currently, no definite therapy and drugs for H. pylori-related GC have been widely acknowledged although H. pylori infection could be eradicated in early stage. Inflammation and immune response are spontaneous essential stages during H. pylori infection. H pylori may mediate immune escape by affecting inflammation and immune response, leading to gastric carcinogenesis. As an important component of transcriptome, non-coding RNAs (ncRNAs) have been proven to play crucial roles in the genesis and development of H. pylori-induced GC. This review briefly described the effects of ncRNAs on H. pylori-related GC from the perspective of inflammation and immune response, as well as their association with inflammatory reaction and immune microenvironment. We aim to explore the potential of ncRNAs as markers for the early diagnosis, prognosis, and treatment of H. pylori-related GC. The ncRNAs involved in H. pylori-related GC may all hold promise as novel therapeutic targets for immunotherapy.
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Affiliation(s)
- Ao-ran Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Zi-wei Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Li-yue Jiang
- Tangdu Hospital of the Fourth Military Medical University, Xi’an, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
- Department of General Surgery, The First Hospital of China Medical University, Shenyang, China
- Zhi Lv,
| | - Yan-ke Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
- Department of General Surgery, The First Hospital of China Medical University, Shenyang, China
- Yan-ke Li,
| | - Ben-gang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
- Department of Hepatobiliary Surgery, Institute of General Surgery, The First Hospital of China Medical University, Shenyang, China
- *Correspondence: Ben-gang Wang,
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26
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Shin CM, Park K, Kim N, Won S, Ohn JH, Lee S, Park JH, Kang SJ, Kim JS, Lee DH. rs2671655 single nucleotide polymorphism modulates the risk for gastric cancer in Helicobacter pylori-infected individuals: a genome-wide association study in the Korean population. Gastric Cancer 2022; 25:573-585. [PMID: 35325318 PMCID: PMC8943788 DOI: 10.1007/s10120-022-01285-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 02/04/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To identify genetic variations which is associated with gastric cancer (GC) risk according to Helicobacter pylori infection. METHODS This study incorporated 527 GC patients and 441 controls from a cohort at Seoul National University Bundang Hospital. The associations between GC risk and single nucleotide polymorphisms were calculated, stratified by H. pylori status, adjusting for age, sex, and smoking. mRNA expression from non-cancerous gastric mucosae was evaluated using reverse transcription quantitative polymerase chain reaction. RESULTS In the entire cohort, genome-wide association study showed no significant variants reached the genome-wide significance level. In the H. pylori-positive group, rs2671655 (chr17:47,468,020;hg19, GH17J049387 enhancer region) was identified at a genome-wide significance level, which was more pronounced in diffuse type GC. There was no significant variant in the H. pylori-negative group, indicating the effect modification of rs2671655 by H. pylori. Among the target genes of GH17J049387 enhancer (PHB1, ZNF652 and SPOP), PHB1 mRNA was expressed more in cases than in controls, who were not affected by H. pylori. By contrast, an increase in ZNF652 and SPOP in GC was observed only in the H. pylori-negative group (P < 0.05). Mediation analysis showed that PHB1 (P = 0.0238) and SPOP (P = 0.0328) mediated the effect of rs2671655 on GC risk. The polygenic risk score was associated with the number of rs2671655 risk alleles only in the H. pylori-positive group (P = 0.0112). CONCLUSION After H. pylori infection, rs2671655 may increase GC risk, especially in diffuse-type GC, by regulating the expression of several genes that consequently modify susceptibility to GC.
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Affiliation(s)
- Cheol Min Shin
- grid.412480.b0000 0004 0647 3378Department of Internal Medicine, Seoul National University Bundang Hospital,, 173-82, Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do 13620 South Korea
| | - Kyungtaek Park
- grid.31501.360000 0004 0470 5905Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Korea
| | - Nayoung Kim
- grid.412480.b0000 0004 0647 3378Department of Internal Medicine, Seoul National University Bundang Hospital,, 173-82, Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do 13620 South Korea ,grid.31501.360000 0004 0470 5905Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sungho Won
- grid.31501.360000 0004 0470 5905Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Korea ,grid.31501.360000 0004 0470 5905Department of Public Health Sciences, Seoul National University, Seoul, South Korea
| | - Jung Hun Ohn
- grid.412480.b0000 0004 0647 3378Department of Internal Medicine, Seoul National University Bundang Hospital,, 173-82, Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do 13620 South Korea
| | - Sejoon Lee
- grid.412480.b0000 0004 0647 3378Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ji Hyun Park
- grid.31501.360000 0004 0470 5905Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Seung Joo Kang
- grid.412484.f0000 0001 0302 820XDepartment of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Joo Sung Kim
- grid.31501.360000 0004 0470 5905Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea ,grid.412484.f0000 0001 0302 820XDepartment of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Dong Ho Lee
- grid.412480.b0000 0004 0647 3378Department of Internal Medicine, Seoul National University Bundang Hospital,, 173-82, Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do 13620 South Korea ,grid.31501.360000 0004 0470 5905Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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Pandey M, Ojha D, Bansal S, Rode AB, Chawla G. From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases. Mol Aspects Med 2021; 81:101003. [PMID: 34332771 DOI: 10.1016/j.mam.2021.101003] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/27/2021] [Accepted: 07/16/2021] [Indexed: 12/14/2022]
Abstract
The functional and structural versatility of Ribonucleic acids (RNAs) makes them ideal candidates for overcoming the limitations imposed by small molecule-based drugs. Hence, RNA-based biopharmaceuticals such as messenger RNA (mRNA) vaccines, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNA mimics, anti-miRNA oligonucleotides (AMOs), aptamers, riboswitches, and CRISPR-Cas9 are emerging as vital tools for the treatment and prophylaxis of many infectious diseases. Some of the major challenges to overcome in the area of RNA-based therapeutics have been the instability of single-stranded RNAs, delivery to the diseased cell, and immunogenicity. However, recent advancements in the delivery systems of in vitro transcribed mRNA and chemical modifications for protection against nucleases and reducing the toxicity of RNA have facilitated the entry of several exogenous RNAs into clinical trials. In this review, we provide an overview of RNA-based vaccines and therapeutics, their production, delivery, current advancements, and future translational potential in treating infectious diseases.
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Affiliation(s)
- Manish Pandey
- RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, 121001, India
| | - Divya Ojha
- Laboratory of Synthetic Biology, Regional Centre for Biotechnology, Faridabad, 121001, India
| | - Sakshi Bansal
- RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, 121001, India
| | - Ambadas B Rode
- Laboratory of Synthetic Biology, Regional Centre for Biotechnology, Faridabad, 121001, India.
| | - Geetanjali Chawla
- RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, 121001, India.
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Non-Coding RNAs and Reactive Oxygen Species–Symmetric Players of the Pathogenesis Associated with Bacterial and Viral Infections. Symmetry (Basel) 2021. [DOI: 10.3390/sym13071307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Infections can be triggered by a wide range of pathogens. However, there are few strains of bacteria that cause illness, but some are quite life-threatening. Likewise, viral infections are responsible for many human diseases, usually characterized by high contagiousness. Hence, as bacterial and viral infections can both cause similar symptoms, it can be difficult to determine the exact cause of a specific infection, and this limitation is critical. However, recent scientific advances have geared us up with the proper tools required for better diagnoses. Recent discoveries have confirmed the involvement of non-coding RNAs (ncRNAs) in regulating the pathogenesis of certain bacterial or viral infections. Moreover, the presence of reactive oxygen species (ROS) is also known as a common infection trait that can be used to achieve a more complete description of such pathogen-driven conditions. Thus, this opens further research opportunities, allowing scientists to explore infection-associated genetic patterns and develop better diagnosis and treatment methods. Therefore, the aim of this review is to summarize the current knowledge of the implication of ncRNAs and ROS in bacterial and viral infections, with great emphasis on their symmetry but, also, on their main differences.
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Liao G, Ma H, Li Y, Sheng Y, Chen C. Selenium nanoparticles inhibit tumor metastasis in prostate cancer through upregulated miR-155-5p-related pathway. Biosci Biotechnol Biochem 2021; 85:287-296. [PMID: 33604641 DOI: 10.1093/bbb/zbaa089] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 08/21/2020] [Indexed: 12/19/2022]
Abstract
Prostate cancer are the most common, malignant and lethal tumors in men, and the complexity of prostate cancer (CaP) is also due to the diverse metastasis profile. Selenium nanoparticles (SeNPs) have been reported to have potent antitumor activity, but whether it impacted the tumor metastasis is not fully clear. Here, we confirmed that SeNPs could inhibit the CaP cell migrations and invasions. Combined with our previous findings, we identified a series of microRNAs that could be upregulated significantly under SeNP treatment, among which miR-155-5p acts as a key component in mediating the SeNP-inhibited migration and invasion of CaP cells, through directly targeting IκB kinase ɛ and Sma- and Mad-related protein 2. The cell-based results were proved in xenograft mice modeling. These results have evidently signified the antitumor potential of SeNPs in the treatment of prostate cancer.
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Affiliation(s)
- Guolong Liao
- Department of Urology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - He Ma
- Department of Urology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Yamei Li
- Department of Urology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Yiyu Sheng
- Department of Urology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Chujie Chen
- Department of Urology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
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30
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Thein W, Po WW, Choi WS, Sohn UD. Autophagy and Digestive Disorders: Advances in Understanding and Therapeutic Approaches. Biomol Ther (Seoul) 2021; 29:353-364. [PMID: 34127572 PMCID: PMC8255139 DOI: 10.4062/biomolther.2021.086] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/11/2021] [Accepted: 05/24/2021] [Indexed: 12/16/2022] Open
Abstract
The gastrointestinal (GI) tract is a series of hollow organs that is responsible for the digestion and absorption of ingested foods and the excretion of waste. Any changes in the GI tract can lead to GI disorders. GI disorders are highly prevalent in the population and account for substantial morbidity, mortality, and healthcare utilization. GI disorders can be functional, or organic with structural changes. Functional GI disorders include functional dyspepsia and irritable bowel syndrome. Organic GI disorders include inflammation of the GI tract due to chronic infection, drugs, trauma, and other causes. Recent studies have highlighted a new explanatory mechanism for GI disorders. It has been suggested that autophagy, an intracellular homeostatic mechanism, also plays an important role in the pathogenesis of GI disorders. Autophagy has three primary forms: macroautophagy, microautophagy, and chaperone-mediated autophagy. It may affect intestinal homeostasis, host defense against intestinal pathogens, regulation of the gut microbiota, and innate and adaptive immunity. Drugs targeting autophagy could, therefore, have therapeutic potential for treating GI disorders. In this review, we provide an overview of current understanding regarding the evidence for autophagy in GI diseases and updates on potential treatments, including drugs and complementary and alternative medicines.
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Affiliation(s)
- Wynn Thein
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Wah Wah Po
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Won Seok Choi
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Uy Dong Sohn
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
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31
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Liu X, Ma R, Yi B, Riker AI, Xi Y. MicroRNAs are involved in the development and progression of gastric cancer. Acta Pharmacol Sin 2021; 42:1018-1026. [PMID: 33037405 PMCID: PMC8208993 DOI: 10.1038/s41401-020-00540-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
MicroRNAs (miRNAs) are recognized as an essential component of the RNA family, exerting multiple and intricate biological functions, particularly in the process of tumorigenesis, proliferation, and metastatic progression. MiRNAs are altered in gastric cancer (GC), showing activity as both tumor suppressors and oncogenes, although their true roles have not been fully understood. This review will focus upon the recent advances of miRNA studies related to the regulatory mechanisms of gastric tumor cell proliferation, apoptosis, and cell cycle. We hope to provide an in-depth insight into the mechanistic role of miRNAs in GC development and progression. In particular, we summarize the latest studies relevant to miRNAs' impact upon the epithelial-mesenchymal transition, tumor microenvironment, and chemoresistance in GC cells. We expect to elucidate the molecular mechanisms involving miRNAs for better understanding the etiology of GC, and facilitating the development of new treatment regimens for the treatment of GC.
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Affiliation(s)
- Xiaolin Liu
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- Department of Oncology, the First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China
| | - Ruixia Ma
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221000, China
| | - Bin Yi
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Adam I Riker
- Geaton and JoAnn DeCesaris Cancer Institute, Department of Surgery, Anne Arundel Medical Center, Cancer Service Line, Luminis Health, Annapolis, MD, USA.
| | - Yaguang Xi
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
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32
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Chang R, Zheng W, Sun Y, Xu T. microRNA-1388-5p inhibits NF-κB signaling pathway in miiuy croaker through targeting IRAK1. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 119:104025. [PMID: 33539892 DOI: 10.1016/j.dci.2021.104025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/20/2021] [Accepted: 01/20/2021] [Indexed: 06/12/2023]
Abstract
Innate immune response is an important response mechanism for the host to achieve self-protection, and it plays an important role in identifying pathogens and resisting pathogen invasion. Growing evidences have shown that microRNA functions as a crucial regulator involved in the host innate immune response. In this study, the regulations of miR-1388-5p to regulate NF-κB signaling pathways via targeting the IRAK1 gene was studied in miiuy croaker. First, through bioinformatics software prediction, we found that IRAK1 is the direct target of miR-1388-5p, and then the prediction results were verified by using dual-luciferase assays. Next, we found that both miR-1388-5p mimics and pre-miR-1388 plasmids inhibit IRAK1 expression by complementing the seed sequence in the 3'-untranslated region (3'-UTR) of IRAK1. Finally, we observed that miR-1388-5p could negatively regulate NF-κB pathways through targeting IRAK1. These results provide new insights into the function of miR-1388-5p in fish innate immunity, meanwhile enriching miRNA-mediated regulatory networks.
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Affiliation(s)
- Renjie Chang
- Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China
| | - Weiwei Zheng
- Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China
| | - Yuena Sun
- Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, 201306, China.
| | - Tianjun Xu
- Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, 201306, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, 201306, China.
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33
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Prinz C, Mese K, Weber D. MicroRNA Changes in Gastric Carcinogenesis: Differential Dysregulation during Helicobacter pylori and EBV Infection. Genes (Basel) 2021; 12:genes12040597. [PMID: 33921696 PMCID: PMC8073778 DOI: 10.3390/genes12040597] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/05/2021] [Accepted: 04/14/2021] [Indexed: 12/11/2022] Open
Abstract
Despite medical advances, gastric-cancer (GC) mortality remains high in Europe. Bacterial infection with Helicobacter pylori (H. pylori) and viral infection with the Epstein–Barr virus (EBV) are associated with the development of both distal and proximal gastric cancer. Therefore, the detection of these infections and the prediction of further cancer development could be clinically significant. To this end, microRNAs (miRNAs) could serve as promising new tools. MiRNAs are highly conserved noncoding RNAs that play an important role in gene silencing, mainly acting via translational repression and the degradation of mRNA targets. Recent reports demonstrate the downregulation of numerous miRNAs in GC, especially miR-22, miR-145, miR-206, miR-375, and miR-490, and these changes seem to promote cancer-cell invasion and tumor spreading. The dysregulation of miR-106b, miR-146a, miR-155, and the Let-7b/c complex seems to be of particular importance during H. pylori infection or gastric carcinogenesis. In contrast, many reports describe changes in host miRNA expression and outline the effects of bamHI-A region rightward transcript (BART) miRNA in EBV-infected tissue. The differential regulation of these miRNA, acting alone or in close interaction when both infections coexist, may therefore enable us to detect cancer earlier. In this review, we focus on the two different etiologies of gastric cancer and outline the molecular pathways through which H. pylori- or EBV-induced changes might synergistically act via miR-155 dysregulation to potentiate cancer risk. The three markers, namely, H. pylori presence, EBV infection, and miR-155 expression, may be checked in routine biopsies to evaluate the risk of developing gastric cancer.
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Affiliation(s)
- Christian Prinz
- Medizinische Klinik 2, Helios Universitätsklinikum Wuppertal, 42283 Wuppertal, Germany;
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
- Correspondence: ; Tel.: +49-202-896-2243; Fax: +49-202-896-2740
| | - Kemal Mese
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
- Institute of Virology, University of Göttingen, 37075 Göttingen, Germany
| | - David Weber
- Medizinische Klinik 2, Helios Universitätsklinikum Wuppertal, 42283 Wuppertal, Germany;
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
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34
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Vasapolli R, Venerito M, Schirrmeister W, Thon C, Weigt J, Wex T, Malfertheiner P, Link A. Inflammatory microRNAs in gastric mucosa are modulated by Helicobacter pylori infection and proton-pump inhibitors but not by aspirin or NSAIDs. PLoS One 2021; 16:e0249282. [PMID: 33857171 PMCID: PMC8049315 DOI: 10.1371/journal.pone.0249282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 03/15/2021] [Indexed: 12/21/2022] Open
Abstract
Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation.
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Affiliation(s)
- Riccardo Vasapolli
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Department of Internal Medicine II, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Wiebke Schirrmeister
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Cosima Thon
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Jochen Weigt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
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35
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Cunningham CC, Wade S, Floudas A, Orr C, McGarry T, Wade S, Cregan S, Fearon U, Veale DJ. Serum miRNA Signature in Rheumatoid Arthritis and "At-Risk Individuals". Front Immunol 2021; 12:633201. [PMID: 33746971 PMCID: PMC7966707 DOI: 10.3389/fimmu.2021.633201] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/11/2021] [Indexed: 12/15/2022] Open
Abstract
Background MicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease in arthralgia or “at-risk individuals”. Methods Serum was collected from HC subjects (N = 20), RA patients (N = 50), and arthralgia subjects (N = 10), in addition to a subgroup of the RA patients post-methotrexate (MTX) (N = 18). The FirePlex miRNA Immunology-V2 panel was selected for multiplex analysis of 68 miRNAs in each sample. DNA intelligent analysis (DIANA)-mirPath and Ingenuity Pathway Analysis (IPA) software were used to predict pathways targeted by the dysregulated miRNAs. Results 8 miRNA (miR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p, miR-339-5p, let-7i-5p) were significantly elevated in RA serum compared to HC (all p < 0.01) and 1 miRNA (miR-17-5p) was significantly lower in RA (p < 0.01). High specificity and sensitivity were determined by receiver operating characteristic (ROC) curve analysis. Both miR-339-5p and let-7i-5p were significantly reduced post-MTX (both p < 0.01). MiR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p were also significantly elevated in subjects “at risk” of developing RA (all p < 0.05) compared to HC. IPA analysis of this miRNA signature identified downstream targets including key transcription factors NF-κB, STAT-1, STAT-3, cytokines IL-1β, TNF-α, and matrix-metalloproteases all importantly associated with RA pathogenesis. Conclusion This study identified six miRNAs that are altered in both RA and “at-risk individuals,” which potentially regulate key downstream pathways involved in regulating inflammation. These may have potential as predictive signature for disease onset and early progression.
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Affiliation(s)
- Clare C Cunningham
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Sarah Wade
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Achilleas Floudas
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Carl Orr
- EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Trudy McGarry
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Siobhan Wade
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Sian Cregan
- EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Ursula Fearon
- Molecular Rheumatology, School of Medicine, Trinity College Dublin, Dublin, Ireland.,EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
| | - Douglas J Veale
- EUropean League Against Rheumatism (EULAR) Centre of Excellence, Centre for Arthritis & Rheumatic Diseases, University College Dublin, Dublin, Ireland
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36
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Riahi Rad Z, Riahi Rad Z, Goudarzi H, Goudarzi M, Mahmoudi M, Yasbolaghi Sharahi J, Hashemi A. MicroRNAs in the interaction between host-bacterial pathogens: A new perspective. J Cell Physiol 2021; 236:6249-6270. [PMID: 33599300 DOI: 10.1002/jcp.30333] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/17/2022]
Abstract
Gene expression regulation plays a critical role in host-pathogen interactions, and RNAs function is essential in this process. miRNAs are small noncoding, endogenous RNA fragments that affect stability and/or translation of mRNAs, act as major posttranscriptional regulators of gene expression. miRNA is involved in regulating many biological or pathological processes through targeting specific mRNAs, including development, differentiation, apoptosis, cell cycle, cytoskeleton organization, and autophagy. Deregulated microRNA expression is associated with many types of diseases, including cancers, immune disturbances, and infection. miRNAs are a vital section of the host immune response to bacterial-made infection. Bacterial pathogens suppress host miRNA expression for their benefit, promoting survival, replication, and persistence. The role played through miRNAs in interaction with host-bacterial pathogen has been extensively studied in the past 10 years, and knowledge about these staggering molecules' function can clarify the complicated and ambiguous interactions of the host-bacterial pathogen. Here, we review how pathogens prevent the host miRNA expression. We briefly discuss emerging themes in this field, including their role as biomarkers in identifying bacterial infections, as part of the gut microbiota, on host miRNA expression.
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Affiliation(s)
- Zohreh Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahmoudi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Javad Yasbolaghi Sharahi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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37
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Săsăran MO, Meliț LE, Dobru ED. MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori. Int J Mol Sci 2021; 22:ijms22031406. [PMID: 33573346 PMCID: PMC7866828 DOI: 10.3390/ijms22031406] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/26/2021] [Accepted: 01/26/2021] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori (H. pylori) remains the most-researched etiological factor for gastric inflammation and malignancies. Its evolution towards gastric complications is dependent upon host immune response. Toll-like receptors (TLRs) recognize surface and molecular patterns of the bacterium, especially the lipopolysaccharide (LPS), and act upon pathways, which will finally lead to activation of the nuclear factor-kappa B (NF-kB), a transcription factor that stimulates release of inflammatory cytokines. MicroRNAs (MiRNAs) finely modulate TLR signaling, but their expression is also modulated by activation of NF-kB-dependent pathways. This review aims to focus upon several of the most researched miRNAs on this subject, with known implications in host immune responses caused by H. pylori, including let-7 family, miRNA-155, miRNA-146, miRNA-125, miRNA-21, and miRNA-221. TLR-LPS interactions and their afferent pathways are regulated by these miRNAs, which can be considered as a bridge, which connects gastric inflammation to pre-neoplastic and malignant lesions. Therefore, they could serve as potential non-invasive biomarkers, capable of discriminating H. pylori infection, as well as its associated complications. Given that data on this matter is limited in children, as well as for as significant number of miRNAs, future research has yet to clarify the exact involvement of these entities in the progression of H. pylori-associated gastric conditions.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics III, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania;
| | - Lorena Elena Meliț
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technol-ogy of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania
- Correspondence: ; Tel.: +40-742-984744
| | - Ecaterina Daniela Dobru
- Department of Internal Medicine VII, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania;
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38
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Chen P, Guo H, Wu X, Li J, Duan X, Ba Q, Wang H. Epigenetic silencing of microRNA-204 by Helicobacter pylori augments the NF-κB signaling pathway in gastric cancer development and progression. Carcinogenesis 2020; 41:430-441. [PMID: 31873718 DOI: 10.1093/carcin/bgz143] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 07/30/2019] [Indexed: 12/22/2022] Open
Abstract
Helicobacter pylori infection induces gastric cancer (GC) development through a progressive cascade; however, the roles of the microRNAs that are involved in the cascade and the underlying mechanisms are still unclear. Here, we found that microRNA-204 was suppressed in gastric mucosal cells in response to H.pylori infection and downregulated in GC tissues due to aberrant methylation of the promoter of its host gene, TRPM3. Helicobacter pylori induced a progressive downregulation of microRNA-204 from superficial gastritis to intestinal metaplasia, with an accompanying increment of the methylated levels of CpG sites in the TRPM3 promoter. With the GC cellular models of AGS, MGC-803 or BGC-823, we found that microRNA-204 suppressed the tumor necrosis factor (TNF)-α-induced activation of NF-κB signaling pathways and, in animal models, inhibited tumor growth and metastasis. The conditional supernatant of microRNA-204 overexpression GC cells led to reduced tube formation of human umbilical vein endothelial cells. A target gene for microRNA-204 was BIRC2, and in GC cells, BIRC2 knockdown recapitulated the biological phenotype of microRNA-204 overexpression. BIRC2 overexpression promoted the metastasis of GC cells and rescued the inhibition activities of microRNA-204 on cell migration and the NF-κB signaling pathway. Moreover, lower microRNA-204 and higher BIRC2 expression levels were associated with a poorer prognosis of GC patients. These results demonstrate that epigenetic silencing of microRNA-204 induced by H.pylori infection augments the NF-κB signaling pathway in H.pylori-induced gastritis and GC, potentially providing novel intervention targets for these diseases. MicroRNA-204 was epigenetically down-regulated by H. pylori infection in gastric mucosal cells. It led to enhanced BIRC2 expression level and BIRC2/TNF-a/NF-kB signaling pathway activities, which promoted angiogenesis and metastasis of gastric cancer cells.
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Affiliation(s)
- Peizhan Chen
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - He Guo
- Key Laboratory of Food Safety Research, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, P. R. China
| | - Xuming Wu
- Nantong Center for Disease Control and Prevention, Nantong, P.R. China.,Nantong Tumor Hospital, Nantong, P. R. China
| | - Jingquan Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Xiaohua Duan
- Key Laboratory of Food Safety Research, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, P. R. China
| | - Qian Ba
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Hui Wang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.,Key Laboratory of Food Safety Research, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, P. R. China
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39
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Tolnai E, Fidler G, Szász R, Rejtő L, Nwozor KO, Biró S, Paholcsek M. Free circulating mircoRNAs support the diagnosis of invasive aspergillosis in patients with hematologic malignancies and neutropenia. Sci Rep 2020; 10:16532. [PMID: 33020578 PMCID: PMC7536194 DOI: 10.1038/s41598-020-73556-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 09/15/2020] [Indexed: 12/15/2022] Open
Abstract
Fungal infections represent a worrisome complication in hematologic cancer patients and in the absence of disease specific symptoms, it is important to establish new biological indicators, which can be used during mould-active prophylaxis. Recently, miRNAs have appeared as candidate diagnostic and prognostic markers of several diseases. A pilot clinical study was performed to evaluate the diagnostic utility of 14 microRNAs which can be related to invasive fungal infections. Based on our data miR-142-3p, miR-142-5p, miR-26b-5p and miR-21-5p showed significant overexpression (p < 0.005) due to invasive aspergillosis in hemato-oncology patients with profound neutropenia. A tetramiR assay was designed to monitor peripheral blood specimens. Optimal cut-off was estimated by using the median value (fold change 1.1) of the log10 transformed gene expressions. The biomarker panel was evaluated on two independent sample cohorts implementing different antimicrobial prophylactic strategies. The receiver operating characteristic analysis with area under the curve proved to be 0.97. Three miRNAs (miR-142-5p, miR-142-3p, miR-16-5p) showed significant expression alterations in episodes with sepsis. In summary, the tetramiR assay proved to be a promising diagnostic adjunct with sufficient accuracy and sensitivity to trace invasive aspergillosis in hemato-oncology patients.
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Affiliation(s)
- Emese Tolnai
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
| | - Gábor Fidler
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
| | - Róbert Szász
- Division of Haematology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - László Rejtő
- Department of Hematology, Jósa András Teaching Hospital, Nyíregyháza, Hungary
| | - Kingsley Okechukwu Nwozor
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
| | - Sándor Biró
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary
| | - Melinda Paholcsek
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary.
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Evaluation of miR-21 Expression Level in Helicobacter pylori-Infected Gastric Mucosa. Jundishapur J Microbiol 2020. [DOI: 10.5812/jjm.100724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Gastric cancer is one of the main causes of death worldwide. In this regard, Helicobacter pylori infection is considered as the main risk factor for gastric cancer. MicroRNA (mirNA) can interface with mRNA molecules as well as blocking their translation into proteins or inducing degradation. Objectives: The aim of this study was to compare the expression of mir-21 in biopsy samples of gastritis and healthy adjacent tissues. Methods: Between Feb-Dec 2017, 70 patients with dyspeptic symptoms from Taleghani Hospital were enrolled in this study. Accordingly, the expression level of mir-21 was evaluated using semi-quantitative RT-PCR in mucosal biopsy samples from those well-characterized patients. Moreover, the U6 gene was used as an internal control. Results: Our data indicated that mir-21 expression was significantly up-regulated in the infected samples with H. pylori compared to healthy samples. Conclusions: Our results confirm that H. pylori infection can alter the expression of mir-21 in gastric epithelial cells and gastric mucosal tissues. However, the exact role of the miRNA changes in H. pylori infection will require further experiments.
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Ebrahimi Ghahnavieh L, Tabatabaeian H, Ebrahimi Ghahnavieh Z, Honardoost MA, Azadeh M, Moazeni Bistgani M, Ghaedi K. Fluctuating expression of miR-584 in primary and high-grade gastric cancer. BMC Cancer 2020; 20:621. [PMID: 32615958 PMCID: PMC7345521 DOI: 10.1186/s12885-020-07116-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 06/25/2020] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics. Methods The expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes. Results Both experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples. Conclusion miR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.
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Affiliation(s)
| | - Hossein Tabatabaeian
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. .,Anahid Cancer Clinic, Isfahan Healthcare City, Isfahan, Iran.
| | - Zhaleh Ebrahimi Ghahnavieh
- Department of Medical Education, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Amin Honardoost
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | | | - Mohamad Moazeni Bistgani
- Department of Surgery, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. .,Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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The Role of MicroRNA in the Airway Surface Liquid Homeostasis. Int J Mol Sci 2020; 21:ijms21113848. [PMID: 32481719 PMCID: PMC7312818 DOI: 10.3390/ijms21113848] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 05/24/2020] [Accepted: 05/25/2020] [Indexed: 02/06/2023] Open
Abstract
Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host-pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.
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Jia Y, Wei Y. Modulators of MicroRNA Function in the Immune System. Int J Mol Sci 2020; 21:E2357. [PMID: 32235299 PMCID: PMC7177468 DOI: 10.3390/ijms21072357] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 03/23/2020] [Accepted: 03/27/2020] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) play a key role in fine-tuning host immune homeostasis and responses through the negative regulation of mRNA stability and translation. The pathways regulated by miRNAs are well characterized, but the precise mechanisms that control the miRNA-mediated regulation of gene expression during immune cell-development and immune responses to invading pathogens are incompletely understood. Context-specific interactions of miRNAs with other RNA species or proteins may modulate the function of a given miRNA. Dysregulation of miRNA function is associated with various human diseases, such as cardiovascular diseases and cancers. Here, we review the potential modulators of miRNA function in the immune system, including the transcription regulators of miRNA genes, miRNA-processing enzymes, factors affecting miRNA targeting, and intercellular communication.
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Affiliation(s)
- Yunhui Jia
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Yuanyuan Wei
- Department of Immunology, Shanghai Key laboratory of Bioactive Small Molecules, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
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44
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Prinz C, Weber D. MicroRNA (miR) dysregulation during Helicobacter pylori-induced gastric inflammation and cancer development: critical importance of miR-155. Oncotarget 2020; 11:894-904. [PMID: 32206186 PMCID: PMC7075464 DOI: 10.18632/oncotarget.27520] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 02/06/2020] [Indexed: 02/03/2023] Open
Abstract
Dysregulation of noncoding microRNA molecules has been associated with immune cell activation in the context of Helicobacter pylori induced gastric inflammation as well as carcinogenesis, but also with downregulation of mismatch repair genes, and may interfere with immune checkpoint proteins that lead to the overexpression of antigens on gastric tumor cells. Numerous miR-molecules have been described as important tools and markers in gastric inflammation and cancer development -including miR-21, miR-143, miR-145, miR-201, and miR-335- all of which are downregulated in gastric tumors, and involved in cell cycle growth or tumor invasion. Among the many microRNAs involved in gastric inflammation, adenocarcinoma development and immune checkpoint regulation, miR-155 is notable in that its upregulation is considered a key marker of chronic gastric inflammation that predisposes a patient to gastric carcinogenesis. Among various other miRs, miR-155 is highly expressed in activated B and T cells and in monocytes/macrophages present in chronic gastric inflammation. Notably, miR-155 was shown to downregulate the expression of certain MMR genes, such as MLH1, MSH2, and MSH6. In tumor-infiltrating miR-155-deficient CD8+ T cells, antibodies against immune checkpoint proteins restored the expression of several derepressed miR-155 targets, suggesting that miR-155 may regulate overlapping pathways to promote antitumor immunity. It may thus be of high clinical impact that gastric pathologies mediated by miR-155 result from its overexpression. This suggests that it may be possible to therapeutically attenuate miR-155 levels for gastric cancer treatment and/or to prevent the progression of chronic gastric inflammation into cancer.
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Affiliation(s)
- Christian Prinz
- Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum, D-42283 Wuppertal, Germany
| | - David Weber
- Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum, D-42283 Wuppertal, Germany
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45
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Yang J, Chen Y, Jiang K, Zhao G, Guo S, Liu J, Yang Y, Deng G. MicroRNA-182 supplies negative feedback regulation to ameliorate lipopolysaccharide-induced ALI in mice by targeting TLR4. J Cell Physiol 2020; 235:5925-5937. [PMID: 32003008 DOI: 10.1002/jcp.29504] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 01/09/2020] [Indexed: 12/20/2022]
Abstract
Acute lung injury (ALI), characterized by increased excessive pulmonary inflammation, is a pervasive inflammatory disease with clinically high incidence. MicroRNA (miRNAs) have been associated with the progression of multiple diseases and are regarded as novel regulators of inflammation. However, it remains largely unknown whether the miRNAs-mediated regulatory mechanism has an effect on lipopolysaccharide (LPS)-induced inflammation in ALI. We discovered that miR-182 distinctly lessened expression in the lung tissue of mice with ALI and macrophages stimulated by LPS. We also found that overexpression of miR-182 significantly cut down the secretion of inflammatory cytokines, while this change was reversed by inhibition of miR-182. In addition, miR-182 suppressed the activation of NF-κB by targeting TLR4 expression. And it was confirmed that miR-182 directly regulated TLR4 expression at the posttranscriptional level by binding to the 3'-UTR of TLR4. Together, these data suggested that inhibition of TLR4 expression assuaged LPS-stimulated inflammation through negative feedback regulation of miR-182.
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Affiliation(s)
- Jing Yang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Yu Chen
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Kangfeng Jiang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Gan Zhao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Shuai Guo
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Junfeng Liu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Yaping Yang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Ganzhen Deng
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
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Dinu AR, Rogobete AF, Bratu T, Popovici SE, Bedreag OH, Papurica M, Bratu LM, Sandesc D. Cannabis Sativa Revisited-Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and Endocannabinoid Response System in Critically Ill Patients with Sepsis. Cells 2020; 9:E307. [PMID: 32012914 PMCID: PMC7072707 DOI: 10.3390/cells9020307] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 01/24/2020] [Accepted: 01/26/2020] [Indexed: 02/06/2023] Open
Abstract
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
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Affiliation(s)
- Anca Raluca Dinu
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
| | - Alexandru Florin Rogobete
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
- Clinic of Anaesthesia and Intensive Care, Emergency County Hospital “Pius Brinzeu”, 325100 Timisoara, Romania
| | - Tiberiu Bratu
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
| | - Sonia Elena Popovici
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
- Clinic of Anaesthesia and Intensive Care, Emergency County Hospital “Pius Brinzeu”, 325100 Timisoara, Romania
| | - Ovidiu Horea Bedreag
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
- Clinic of Anaesthesia and Intensive Care, Emergency County Hospital “Pius Brinzeu”, 325100 Timisoara, Romania
| | - Marius Papurica
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
- Clinic of Anaesthesia and Intensive Care, Emergency County Hospital “Pius Brinzeu”, 325100 Timisoara, Romania
| | - Lavinia Melania Bratu
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
| | - Dorel Sandesc
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.R.D.); (A.F.R.); (S.E.P.); (M.P.); (L.M.B.); (D.S.)
- Clinic of Anaesthesia and Intensive Care, Emergency County Hospital “Pius Brinzeu”, 325100 Timisoara, Romania
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Ding S, Liu G, Jiang H, Fang J. MicroRNA Determines the Fate of Intestinal Epithelial Cell Differentiation and Regulates Intestinal Diseases. Curr Protein Pept Sci 2019; 20:666-673. [PMID: 30678626 DOI: 10.2174/1389203720666190125110626] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 12/30/2018] [Accepted: 01/10/2019] [Indexed: 12/19/2022]
Abstract
The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.
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Affiliation(s)
- Sujuan Ding
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, China.,Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan, China.,Academician Workstation of Hunan Baodong Farming Co., Ltd., Hunan 422001, China
| | - Gang Liu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, China.,Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan, China
| | - Hongmei Jiang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, China
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, China
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48
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Yousefi B, Mohammadlou M, Abdollahi M, Salek Farrokhi A, Karbalaei M, Keikha M, Kokhaei P, Valizadeh S, Rezaiemanesh A, Arabkari V, Eslami M. Epigenetic changes in gastric cancer induction by Helicobacter pylori. J Cell Physiol 2019; 234:21770-21784. [PMID: 31169314 DOI: 10.1002/jcp.28925] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 05/06/2019] [Accepted: 05/07/2019] [Indexed: 02/05/2023]
Abstract
Epigenetic disorder mechanisms are one of the causes of cancer. The most important of these changes is the DNA methylation, which leads to the spread of Helicobacter pylori and inflammatory processes followed by induction of DNA methylation disorder. Mutations and epigenetic changes are the two main agents of neoplasia. Epithelial cells infection by H. pylori associated with activating several intracellular pathways including: MAPK, NF-κB, Wnt/β-catenin, and PI3K are affects a variety of cells and caused to an increase in the production of inflammatory cytokines, changes in apoptosis, proliferation, differentiation, and ultimately leads to the transformation of epithelial cells into oncogenic. The arose of free radicals impose the DNA cytosine methylation, and NO can increase the activity of DNA methyltransferase. H. pylori infection causes an environment that mediates inflammation and signaling pathways that probably caused to stomach tumorigenicity. The main processes that change by decreasing or increasing the expression of various microRNAs expressions include immune responses, apoptosis, cell cycle, and autophagy. In this review will be describe a probably H. pylori roles in infection and mechanisms that have contribution in epigenetic changes in the promoter of genes.
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Affiliation(s)
- Bahman Yousefi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Maryam Mohammadlou
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Maryam Abdollahi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Amir Salek Farrokhi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Masoud Keikha
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parviz Kokhaei
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
- Immune and Gene Therapy Lab, Cancer Centre Karolinska, Karolinska University Hospital, Stockholm, Sweden
| | - Saeid Valizadeh
- Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran
| | - Alireza Rezaiemanesh
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Vahid Arabkari
- Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland
| | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
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Zhang F, Chen C, Hu J, Su R, Zhang J, Han Z, Chen H, Li Y. Molecular mechanism of Helicobacter pylori-induced autophagy in gastric cancer. Oncol Lett 2019; 18:6221-6227. [PMID: 31788098 DOI: 10.3892/ol.2019.10976] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 07/26/2019] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells. The drug resistance rates of H. pylori have dramatically increased, causing persistent infections. Chronic infection by H. pylori is a critical cause of gastritis, peptic ulcers and even gastric cancer. In host cells, autophagy is stimulated to maintain cellular homeostasis following intracellular pathogen recognition by the innate immune defense system. However, H. pylori-induced autophagy is not consistent during acute and chronic infection. Therefore, a deeper understanding of the association between H. pylori infection and autophagy in gastric epithelial cells could aid the understanding of the mechanisms of persistent infection and the identification of autophagy-associated therapeutic targets for H. pylori infection. The present review describes the role of H. pylori and associated virulence factors in the induction of autophagy by different signaling pathways during acute infection. Additionally, the inhibition of autophagy in gastric epithelial cells during chronic infection was discussed. The present review summarized H. pylori-mediated autophagy and provided insights into its mechanism of action, suggesting the induction of autophagy as a novel therapeutic target for persistent H. pylori infection.
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Affiliation(s)
- Fan Zhang
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Cong Chen
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Jike Hu
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Ruiliang Su
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Junqiang Zhang
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Zhijian Han
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Hao Chen
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
| | - Yumin Li
- Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
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50
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Su T, Li F, Guan J, Liu L, Huang P, Wang Y, Qi X, Liu Z, Lu L, Wang D. Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 63:152968. [PMID: 31280140 DOI: 10.1016/j.phymed.2019.152968] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 04/30/2019] [Accepted: 05/21/2019] [Indexed: 05/21/2023]
Abstract
BACKGROUND Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.
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Key Words
- ARTS, artesunate
- Abbreviations: ART, artemisinin
- Artemisinin
- Artesunate
- CFU, colony forming units
- COX-2, cyclooxygenase-2
- DHA, dehydroartemisinin
- DMSO, dimethyl sulfoxide
- Dihydroartemisinin
- ELISA, enzyme-linked immunosorbent assay
- Gastric cancer
- Helicobacter pylori
- IARC, International Agency for Research on Cancer
- IL-8, interleukin-8
- MNU, N-methyl-N-nitroso-urea
- MOI, multiplicity of infection
- NF-κB signaling
- NF-κB, nuclear factor-κB
- PBS, phosphate buffer solution
- ROS, reactive oxygen species
- TNF-α, tumor necrosis factor-α
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Affiliation(s)
- Tao Su
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Fangyuan Li
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Jiaji Guan
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Linxin Liu
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ping Huang
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ying Wang
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xiaoxiao Qi
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhongqiu Liu
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Linlin Lu
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Dawei Wang
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China.
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