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Aytekin A, Kadakal H, Mihcioglu D, Gurer T. Bioinformatics analysis of miR-2861 and miR-5011-5p that function as potential tumor suppressors in colorectal carcinogenesis. BMC Med Genomics 2025; 18:1. [PMID: 39748239 PMCID: PMC11697744 DOI: 10.1186/s12920-024-02080-6] [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: 06/25/2024] [Accepted: 12/26/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND The study aimed to was to investigate the relationship between miR-2861, miR-5011-5p, and colorectal carcinogenesis. METHOD In the present study, it was isolated RNA from both the tumor and non-tumor tissue of a total of 80 CRC patients and after synthesizing the cDNA, it was performed qRT-PCR to determine the expression levels of miR‑2861 and miR‑5011-5p. In addition, it was predicted that dysregulated miRNAs targets, pathways and functional gene annotations that may be important in colorectal carcinogenesis using KEGG pathway and GO analysis. RESULTS The resulting data revealed that both expression levels of miR-2861 and miR-5011-5p were significantly decreased in tumor tissues compared with non-tumor tissues of CRC patients. The GO and KEGG pathway analysis showed that miR-2861 and miR-5011-5p may participate in multiple the biological process, cellular components, and molecular function subcategories such as mitotic cell cycle, regulation of small GTPase mediated signal transduction, cell death, and acid binding transcription factor activity. It was also revealed that target genes of miRNAs can be found in signaling pathways such as TGF-beta, Rap1, Ras, cAMP, Wnt, mTOR and, PI3K-Akt signaling pathways. CONCLUSION These findings imply that miR-2861 and miR-5011-5p might function as tumor suppressors in the development of CRC.
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Affiliation(s)
- Alper Aytekin
- Department of General Surgery, Faculty of Medicine, Gaziantep University, Gaziantep, 27310, Turkey.
| | - Hikmet Kadakal
- Department of Biology, Faculty of Art and Science, Gaziantep University, Gaziantep, 27310, Turkey
| | - Deniz Mihcioglu
- Department of Nutrition and Dietetics, Faculty of Health Science, SANKO University, Gaziantep, 27090, Turkey
| | - Turkan Gurer
- Department of Biology, Faculty of Art and Science, Gaziantep University, Gaziantep, 27310, Turkey
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Yadav V, Singh T, Sharma D, Garg VK, Chakraborty P, Ghatak S, Satapathy SR. Unraveling the Regulatory Role of HuR/microRNA Axis in Colorectal Cancer Tumorigenesis. Cancers (Basel) 2024; 16:3183. [PMID: 39335155 PMCID: PMC11430344 DOI: 10.3390/cancers16183183] [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: 08/07/2024] [Revised: 09/04/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health burden with high incidence and mortality. MicroRNAs (miRNAs) are small non-protein coding transcripts, conserved throughout evolution, with an important role in CRC tumorigenesis, and are either upregulated or downregulated in various cancers. RNA-binding proteins (RBPs) are known as essential regulators of miRNA activity. Human antigen R (HuR) is a prominent RBP known to drive tumorigenesis with a pivotal role in CRC. In this review, we discuss the regulatory role of the HuR/miRNA axis in CRC. Interestingly, miRNAs can directly target HuR, altering its expression and activity. However, HuR can also stabilize or degrade miRNAs, forming complex feedback loops that either activate or block CRC-associated signaling pathways. Dysregulation of the HuR/miRNA axis contributes to CRC initiation and progression. Additionally, HuR-miRNA regulation by other small non-coding RNAs, circular RNA (circRNAs), or long-non-coding RNAs (lncRNAs) is also explored here. Understanding this HuR-miRNA interplay could reveal novel biomarkers with better diagnostic or prognostic accuracy.
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Affiliation(s)
- Vikas Yadav
- Department of Translational Medicine, Clinical Research Centre, Lund University, 221 00 Malmö, Sweden;
| | - Tejveer Singh
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, University of Delhi, New Delhi 110021, India; (T.S.); (D.S.)
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS-DRDO), New Delhi 110054, India
| | - Deepika Sharma
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, University of Delhi, New Delhi 110021, India; (T.S.); (D.S.)
| | - Vivek Kumar Garg
- Department of Medical Lab Technology, Chandigarh University, Gharuan, Mohali 140413, Punjab, India;
| | - Payel Chakraborty
- Amity Institute of Biotechnology, Amity University Kolkata, Kolkata 700135, West Bengal, India; (P.C.); (S.G.)
| | - Souvik Ghatak
- Amity Institute of Biotechnology, Amity University Kolkata, Kolkata 700135, West Bengal, India; (P.C.); (S.G.)
| | - Shakti Ranjan Satapathy
- Department of Translational Medicine, Clinical Research Centre, Lund University, 221 00 Malmö, Sweden;
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Wu T, Lu ZF, Yu HN, Wu XS, Liu Y, Xu Y. Liver receptor homolog-1: structures, related diseases, and drug discovery. Acta Pharmacol Sin 2024; 45:1571-1581. [PMID: 38632319 PMCID: PMC11272790 DOI: 10.1038/s41401-024-01276-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 03/24/2024] [Indexed: 04/19/2024]
Abstract
Liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is a ligand-regulated transcription factor that plays crucial roles in metabolism, development, and immunity. Despite being classified as an 'orphan' receptor due to the ongoing debate surrounding its endogenous ligands, recent researches have demonstrated that LRH-1 can be modulated by various synthetic ligands. This highlights the potential of LRH-1 as an attractive drug target for the treatment of inflammation, metabolic disorders, and cancer. In this review, we provide an overview of the structural basis, functional activities, associated diseases, and advancements in therapeutic ligand research targeting LRH-1.
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Affiliation(s)
- Tong Wu
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China
- State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China
| | - Zhi-Fang Lu
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China
- State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China
| | - Hao-Nan Yu
- State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China
| | - Xi-Shan Wu
- State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China
| | - Yang Liu
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Yong Xu
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
- State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China.
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4
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Cao Y, Lu C, Beeraka NM, Efetov S, Enikeev M, Fu Y, Yang X, Basappa B, He M, Li Z. Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation. Front Immunol 2024; 15:1428920. [PMID: 39015566 PMCID: PMC11249567 DOI: 10.3389/fimmu.2024.1428920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/14/2024] [Indexed: 07/18/2024] Open
Abstract
Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplay between anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development.
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Affiliation(s)
- Yu Cao
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Chang Lu
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Narasimha M. Beeraka
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
- Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
- Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Chiyyedu, Andhra Pradesh, India
| | - Sergey Efetov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Mikhail Enikeev
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Yu Fu
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Xinyi Yang
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Basappa Basappa
- Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore, Karnataka, India
| | - Mingze He
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Zhi Li
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
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Cao Y, Lu C, Beeraka NM, Efetov S, Enikeev M, Fu Y, Yang X, Basappa B, He M, Li Z. Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation. Front Immunol 2024; 15. [DOI: https:/doi.org/10.3389/fimmu.2024.1428920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2024] Open
Abstract
Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplay between anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development.
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6
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Nguyen DH, Uddin MJ, Al-Tawfiq JA, Memish ZA, Chu DT. RNA therapeutics for diarrhea. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 204:295-309. [PMID: 38458741 DOI: 10.1016/bs.pmbts.2023.12.004] [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: 03/10/2024]
Abstract
Diarrhea is caused by a variety of bacterial and viral agents, inflammatory conditions, medications, and hereditary conditions. Secretory diarrhea involves several ion and solute transporters, activation of the cyclic nucleotide and Ca2+ signaling pathways, as well as intestinal epithelial secretion. In many cases of secretory diarrhea, activation of Cl- channels, such as the cystic transmembrane conduction regulator and the Ca2+stimulated Cl- channel fibrosis, promote secretion while concurrently inhibiting Na+ transport expressing fluid absorption. Current diarrhea therapies include rehydration and electrolyte replacement via oral rehydration solutions, as well as medications that target peristalsis or fluid secretion. The rising understanding of RNA function and its importance in illness has encouraged the use of various RNAs to operate selectively on "untreatable" proteins, transcripts, and genes. Some RNA-based medications have received clinical approval, while others are currently in research or preclinical studies. Despite major obstacles in the development of RNA-based therapies, many approaches have been investigated to improve intracellular RNA trafficking and metabolic stability.
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Affiliation(s)
| | - Md Jamal Uddin
- ABEx Bio-Research Center, East Azampur, Dhaka, Bangladesh; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
| | - Jaffar A Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia; Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States; Infectious Disease Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Ziad A Memish
- Director Research and Innovation Centre, King Saud Medical City, Ministry of Health and College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Dinh-Toi Chu
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam; Faculty of Applied Sciences, International School, Vietnam National University, Hanoi, Vietnam.
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Yang B, Lin Y, Huang Y, Zhu N, Shen YQ. Extracellular vesicles modulate key signalling pathways in refractory wound healing. BURNS & TRAUMA 2023; 11:tkad039. [PMID: 38026441 PMCID: PMC10654481 DOI: 10.1093/burnst/tkad039] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 05/10/2023] [Accepted: 06/22/2023] [Indexed: 12/01/2023]
Abstract
Chronic wounds are wounds that cannot heal properly due to various factors, such as underlying diseases, infection or reinjury, and improper healing of skin wounds and ulcers can cause a serious economic burden. Numerous studies have shown that extracellular vesicles (EVs) derived from stem/progenitor cells promote wound healing, reduce scar formation and have significant advantages over traditional treatment methods. EVs are membranous particles that carry various bioactive molecules from their cellular origins, such as cytokines, nucleic acids, enzymes, lipids and proteins. EVs can mediate cell-to-cell communication and modulate various physiological processes, such as cell differentiation, angiogenesis, immune response and tissue remodelling. In this review, we summarize the recent advances in EV-based wound healing, focusing on the signalling pathways that are regulated by EVs and their cargos. We discuss how EVs derived from different types of stem/progenitor cells can promote wound healing and reduce scar formation by modulating the Wnt/β-catenin, phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin, vascular endothelial growth factor, transforming growth factor β and JAK-STAT pathways. Moreover, we also highlight the challenges and opportunities for engineering or modifying EVs to enhance their efficacy and specificity for wound healing.
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Affiliation(s)
- Bowen Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Wuhou District, Chengdu 610041, China
| | - Yumeng Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Wuhou District, Chengdu 610041, China
| | - Yibo Huang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Wuhou District, Chengdu 610041, China
| | - Nanxi Zhu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Wuhou District, Chengdu 610041, China
| | - Ying-Qiang Shen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Wuhou District, Chengdu 610041, China
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Fattahi M, Shahrabi S, Saadatpour F, Rezaee D, Beyglu Z, Delavari S, Amrolahi A, Ahmadi S, Bagheri-Mohammadi S, Noori E, Majidpoor J, Nouri S, Aghaei-Zarch SM, Falahi S, Najafi S, Le BN. microRNA-382 as a tumor suppressor? Roles in tumorigenesis and clinical significance. Int J Biol Macromol 2023; 250:125863. [PMID: 37467828 DOI: 10.1016/j.ijbiomac.2023.125863] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/30/2023] [Accepted: 07/15/2023] [Indexed: 07/21/2023]
Abstract
MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.
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Affiliation(s)
- Mehdi Fattahi
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam; School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
| | - Saeid Shahrabi
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Saadatpour
- Pharmaceutical Biotechnology Lab, Department of Microbiology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
| | - Delsuz Rezaee
- School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
| | - Zahra Beyglu
- Department of Genetics, Qom Branch, Islamic Azad University, Qom, Iran
| | - Sana Delavari
- Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Anita Amrolahi
- Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Shirin Ahmadi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Bagheri-Mohammadi
- Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Effat Noori
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Shadi Nouri
- Department of Radiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
| | - Seyed Mohsen Aghaei-Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Shahab Falahi
- Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Binh Nguyen Le
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam; School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
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Collins KE, Wang X, Klymenko Y, Davis NB, Martinez MC, Zhang C, So K, Buechlein A, Rusch DB, Creighton CJ, Hawkins SM. Transcriptomic analyses of ovarian clear-cell carcinoma with concurrent endometriosis. Front Endocrinol (Lausanne) 2023; 14:1162786. [PMID: 37621654 PMCID: PMC10445169 DOI: 10.3389/fendo.2023.1162786] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 07/17/2023] [Indexed: 08/26/2023] Open
Abstract
Introduction Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC). Methods To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing. Results Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment analysis showed upregulation of pathways involved in cell cycle regulation and DNA replication and downregulation of pathways involved in cytokine receptor signaling and matrisome. Comparison of pathway activation scores between the clinical samples and publicly-available datasets for OCCC cell lines revealed significant molecular similarities between OCCC with concurrent endometriosis and OVTOKO, OVISE, RMG1, OVMANA, TOV21G, IGROV1, and JHOC5 cell lines. Analysis of miRNAs revealed 64 upregulated and 61 downregulated mature miRNA molecules (DESeq2, P< 0.05, log2 fold-change > |1|). MiR-10a-5p represented over 21% of the miRNA molecules in OCCC with endometriosis and was significantly upregulated (NGS: log2fold change = 4.37, P = 2.43e-18; QPCR: 8.1-fold change, P< 0.05). Correlation between miR-10a expression level in OCCC cell lines and IC50 (50% inhibitory concentration) of carboplatin in vitro revealed a positive correlation (R2 = 0.93). MiR-10a overexpression in vitro resulted in a significant decrease in proliferation (n = 6; P< 0.05) compared to transfection with a non-targeting control miRNA. Similarly, the cell-cycle analysis revealed a significant shift in cells from S and G2 to G1 (n = 6; P< 0.0001). Bioinformatic analysis predicted that miR-10a-5p target genes that were downregulated in OCCC with endometriosis were involved in receptor signaling pathways, proliferation, and cell cycle progression. MiR-10a overexpression in vitro was correlated with decreased expression of predicted miR-10a target genes critical for proliferation, cell-cycle regulation, and cell survival including [SERPINE1 (3-fold downregulated; P< 0.05), CDK6 (2.4-fold downregulated; P< 0.05), and RAP2A (2-3-fold downregulated; P< 0.05)]. Discussion These studies in OCCC suggest that miR-10a-5p is an impactful, potentially oncogenic molecule, which warrants further studies.
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Affiliation(s)
- Kaitlyn E. Collins
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Xiyin Wang
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, United States
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Yuliya Klymenko
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Noah B. Davis
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Maria C. Martinez
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Chi Zhang
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
- Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Kaman So
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
- Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Aaron Buechlein
- Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN, United States
| | - Douglas B. Rusch
- Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN, United States
| | - Chad J. Creighton
- Department of Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Shannon M. Hawkins
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, United States
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10
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Wang R, Wang Y, Liu X, Liu M, Sun L, Pan X, Hu H, Jiang B, Zou Y, Liu Q, Gong Y, Wang M, Sun G. Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling. Cell Death Dis 2023; 14:388. [PMID: 37391410 PMCID: PMC10313691 DOI: 10.1038/s41419-023-05916-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 06/15/2023] [Accepted: 06/21/2023] [Indexed: 07/02/2023]
Abstract
Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal cancer cells can undergo anastasis after transient exposure to chemotherapeutic drugs. Using a lineage tracing system to label and isolate cells that have experienced executioner caspase activation in response to drug treatment, we show that anastasis grants colorectal cancer cells enhanced migration, metastasis, and chemoresistance. Mechanistically, treatment with chemotherapeutic drugs induces upregulated expression of cIAP2 and activation of NFκB, which are required for cells to survive executioner caspase activation. The elevated cIAP2/NFκB signaling persists in anastatic cancer cells to promote migration and chemoresistance. Our study unveils that cIAP2/NFκB-dependent anastasis promotes acquired resistance and metastasis after chemotherapy.
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Affiliation(s)
- Ru Wang
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Yuxing Wang
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Xiaohe Liu
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Menghao Liu
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Lili Sun
- Key Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Xiaohua Pan
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Huili Hu
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
- Department of Systems Biomedicine and Research Center of Stem Cell and Regenerative Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Baichun Jiang
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Yongxin Zou
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Qiao Liu
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Yaoqin Gong
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Molin Wang
- Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
| | - Gongping Sun
- Key Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
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11
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Prendecka-Wróbel M, Pigoń-Zając D, Sondej D, Grzywna K, Kamińska K, Szuta M, Małecka-Massalska T. Can Dietary Actives Affect miRNAs and Alter the Course or Prevent Colorectal Cancer? Int J Mol Sci 2023; 24:10142. [PMID: 37373289 DOI: 10.3390/ijms241210142] [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: 04/24/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Colorectal cancer is a diet-related cancer. There is much research into the effects of nutrients on the prevention, modulation, and treatment of colorectal cancer. Researchers are trying to find a correlation between epidemiological observations indicating certain dietary components as the originator in the process of developing colorectal cancer, such as a diet rich in saturated animal fats, and dietary components that could eliminate the impact of harmful elements of the daily nutritional routine, i.e., substances such as polyunsaturated fatty acids, curcumin, or resveratrol. Nevertheless, it is very important to understand the mechanisms underlying how food works on cancer cells. In this case, microRNA (miRNA) seems to be a very significant research target. MiRNAs participate in many biological processes connected to carcinogenesis, progression, and metastasis. However, this is a field with development prospects ahead. In this paper, we review the most significant and well-studied food ingredients and their effects on various miRNAs involved in colorectal cancer.
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Affiliation(s)
- Monika Prendecka-Wróbel
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Dominika Pigoń-Zając
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Daria Sondej
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Karolina Grzywna
- Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Katarzyna Kamińska
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Mariusz Szuta
- Chair of Oral Surgery, Jagiellonian University Medical College, 31-155 Kraków, Poland
| | - Teresa Małecka-Massalska
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
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12
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Chandramohan K, Balan DJ, Devi KP, Nabavi SF, Reshadat S, Khayatkashani M, Mahmoodifar S, Filosa R, Amirkhalili N, Pishvaei S, Aval OS, Nabavi SM. Short interfering RNA in colorectal cancer: is it wise to shoot the messenger? Eur J Pharmacol 2023; 949:175699. [PMID: 37011722 DOI: 10.1016/j.ejphar.2023.175699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 03/23/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023]
Abstract
Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/β-catenin, transforming growth factor-β (TNF-β), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.
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13
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Xie Y, Zhang Y, Liu X, Cao L, Han M, Wang C, Chen J, Zhang X. miR‑151a‑5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT. Oncol Rep 2023; 49:50. [PMID: 36704851 PMCID: PMC9887461 DOI: 10.3892/or.2023.8487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 01/11/2023] [Indexed: 01/22/2023] Open
Abstract
Colorectal carcinoma (CRC) is one of the most common types of digestive cancer. It has been reported that the ectopic expression of microRNAs (miRs) plays a critical role in the occurrence and progression of CRC. In addition, it has also been suggested that miR‑151a‑5p may serve as a useful biomarker for the early detection and treatment of different types of cancer and particularly CRC. However, the specific effects and underlying mechanisms of miR‑151a‑5p in CRC remain elusive. The results of the current study demonstrated that miR‑151a‑5p was upregulated in CRC cell lines and clinical tissues derived from patients with CRC. Functionally, the results showed that miR‑151a‑5p significantly promoted CRC cell proliferation, migration and invasion. Additionally, dual luciferase reporter assays verified that agmatinase (AGMAT) was a direct target of miR‑151a‑5p and it was positively associated with miR‑151a‑5p expression. Mechanistically, miR‑151a‑5p could enhance the epithelial‑mesenchymal transition of CRC cells. Taken together, the results of the current study revealed a novel molecular mechanism indicating that the miR‑151a‑5p/AGMAT axis could serve a crucial role in the regulation of CRC and could therefore be considered as a potential therapeutic strategy for CRC.
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Affiliation(s)
- Yaya Xie
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Yue Zhang
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
- Hanzhong Central Hospital of Shaanxi, Hanzhong, Shaanxi 723000, P.R. China
| | - Xianju Liu
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Lijun Cao
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Mengting Han
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Chunmei Wang
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
| | - Jinlian Chen
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
| | - Xingxing Zhang
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
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14
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Circulating Biomarkers for Cancer Detection: Could Salivary microRNAs Be an Opportunity for Ovarian Cancer Diagnostics? Biomedicines 2023; 11:biomedicines11030652. [PMID: 36979630 PMCID: PMC10044752 DOI: 10.3390/biomedicines11030652] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 02/02/2023] [Accepted: 02/16/2023] [Indexed: 02/24/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs with the crucial regulatory functions of gene expression at post-transcriptional level, detectable in cell and tissue extracts, and body fluids. For their stability in body fluids and accessibility to sampling, circulating miRNAs and changes of their concentration may represent suitable disease biomarkers, with diagnostic and prognostic relevance. A solid literature now describes the profiling of circulating miRNA signatures for several tumor types. Among body fluids, saliva accurately reflects systemic pathophysiological conditions, representing a promising diagnostic resource for the future of low-cost screening procedures for systemic diseases, including cancer. Here, we provide a review of literature about miRNAs as potential disease biomarkers with regard to ovarian cancer (OC), with an excursus about liquid biopsies, and saliva in particular. We also report on salivary miRNAs as biomarkers in oncological conditions other than OC, as well as on OC biomarkers other than miRNAs. While the clinical need for an effective tool for OC screening remains unmet, it would be advisable to combine within a single diagnostic platform, the tools for detecting patterns of both protein and miRNA biomarkers to provide the screening robustness that single molecular species separately were not able to provide so far.
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15
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Das PK, Saha J, Pillai S, Lam AKY, Gopalan V, Islam F. Implications of estrogen and its receptors in colorectal carcinoma. Cancer Med 2023; 12:4367-4379. [PMID: 36207986 PMCID: PMC9972078 DOI: 10.1002/cam4.5242] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/18/2022] [Accepted: 09/01/2022] [Indexed: 11/08/2022] Open
Abstract
Estrogens have been implicated in the pathogenesis of various cancer types, including colorectal carcinoma (CRC). Estrogen receptors such as ERα and ERβ activate intracellular signaling cascades followed by binding to estrogen, resulting in important changes in cellular behaviors. The nuclear estrogen receptors, i.e. ERβ and ERα are responsible for the genomic actions of estrogens, whereas the other receptor, such as G protein-coupled estrogen receptor (GPER) regulates rapid non-genomic actions, which lead to secondary gene expression changes in cells. ERβ, the predominant estrogen receptor expressed in both normal and non-malignant colonic epithelium, has protective roles in colon carcinogenesis. ERβ may exert the anti-tumor effect through selective activation of pro-apoptotic signaling, increasing DNA repair, inhibiting expression of oncogenes, regulating cell cycle progression, and also by changing the micro-RNA pool and DNA-methylation. Thus, a better understanding of the underlying mechanisms of estrogen and its receptors in CRC pathogenesis could provide a new horizon for effective therapeutic development. Furthermore, using synthetic or natural compounds as ER agonists may induce estrogen-mediated anti-cancer activities against colon cancer. In this study, we report the most recent pre-clinical and experimental evidences related to ERs in CRC development. Also, we reviewed the actions of naturally occurring and synthetic compounds, which have a protective role against CRC development by acting as ER agonist.
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Affiliation(s)
- Plabon Kumar Das
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.,Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
| | - Joti Saha
- Department of Applied Chemistry and Chemical Engineering, University of Rajshahi, Rajshahi, Bangladesh
| | - Suja Pillai
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Alfred K-Y Lam
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia
| | - Vinod Gopalan
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia
| | - Farhadul Islam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.,Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
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16
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Losurdo P, Gandin I, Belgrano M, Fiorese I, Verardo R, Zanconati F, Cova MA, de Manzini N. microRNAs combined to radiomic features as a predictor of complete clinical response after neoadjuvant radio-chemotherapy for locally advanced rectal cancer: a preliminary study. Surg Endosc 2023; 37:3676-3683. [PMID: 36639577 DOI: 10.1007/s00464-022-09851-1] [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: 07/18/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To define a predictive Artificial Intelligence (AI) algorithm based on the integration of a set of biopsy-based microRNAs expression data and radiomic features to understand their potential impact in predicting clinical response (CR) to neoadjuvant radio-chemotherapy (nRCT). The identification of patients who would truly benefit from nRCT for Locally Advanced Rectal Cancer (LARC) could be crucial for an improvement in a tailored therapy. METHODS Forty patients with LARC were retrospectively analyzed. An MRI of the pelvis before and after nRCT was performed. In the diagnostic biopsy, the expression levels of 7 miRNAs were measured and correlated with the tumor response rate (TRG), assessed on the surgical sample. The accuracy of complete CR (cCR) prediction was compared for i) clinical predictors; ii) radiomic features; iii) miRNAs levels; and iv) combination of radiomics and miRNAs. RESULTS Clinical predictors showed the lowest accuracy. The best performing model was based on the integration of radiomic features with miR-145 expression level (AUC-ROC = 0.90). AI algorithm, based on radiomics features and the overexpression of miR-145, showed an association with the TRG class and demonstrated a significant impact on the outcome. CONCLUSION The pre-treatment identification of responders/NON-responders to nRCT could address patients to a personalized strategy, such as total neoadjuvant therapy (TNT) for responders and upfront surgery for non-responders. The combination of radiomic features and miRNAs expression data from images and biopsy obtained through standard of care has the potential to accelerate the discovery of a noninvasive multimodal approach to predict the cCR after nRCT for LARC.
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Affiliation(s)
- Pasquale Losurdo
- Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy.
| | - Ilaria Gandin
- Biostatistics Unit, Department of Medical and Surgical Sciences, University of Trieste, Strada Di Fiume 447, 34149, Trieste, Italy
| | - Manuel Belgrano
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Ilaria Fiorese
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Roberto Verardo
- LNCIB - Consorzio Interuniversitario per le Biotecnologie c/o BIC Incubatori FVG, Srl - Via Flavia 23/1, 34149, Trieste, Italy
| | - Fabrizio Zanconati
- Pathology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Maria Assunta Cova
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Nicolò de Manzini
- Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
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17
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Ko B, Hanna M, Yu M, Grady WM. Epigenetic Alterations in Colorectal Cancer. EPIGENETICS AND HUMAN HEALTH 2023:331-361. [DOI: 10.1007/978-3-031-42365-9_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Tang F, Liu Y, Sun Y, Xiong Y, Gu Y, Zhou J, Ouyang Y, Zhang S. Construction of a serum diagnostic signature based on m5C-related miRNAs for cancer detection. Front Endocrinol (Lausanne) 2023; 14:1099703. [PMID: 36777349 PMCID: PMC9911864 DOI: 10.3389/fendo.2023.1099703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/13/2023] [Indexed: 01/28/2023] Open
Abstract
Currently, no clinically relevant non-invasive biomarkers are available for screening of multiple cancer types. In this study, we developed a serum diagnostic signature based on 5-methylcytosine (m5C)-related miRNAs (m5C-miRNAs) for multiple-cancer detection. Serum miRNA expression data and the corresponding clinical information of patients were collected from the Gene Expression Omnibus database. Serum samples were then randomly assigned to the training or validation cohort at a 1:1 ratio. Using the identified m5C-miRNAs, an m5C-miRNA signature for cancer detection was established using a support vector machine algorithm. The constructed m5C-miRNA signature displayed excellent accuracy, and its areas under the curve were 0.977, 0.934, and 0.965 in the training cohort, validation cohort, and combined training and validation cohort, respectively. Moreover, the diagnostic capability of the m5C-miRNA signature was unaffected by patient age or sex or the presence of noncancerous disease. The m5C-miRNA signature also displayed satisfactory performance for distinguishing tumor types. Importantly, in the detection of early-stage cancers, the diagnostic performance of the m5C-miRNA signature was obviously superior to that of conventional tumor biomarkers. In summary, this work revealed the value of serum m5C-miRNAs in cancer detection and provided a new strategy for developing non-invasive and cost effective tools for large-scale cancer screening.
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Affiliation(s)
- Fuzhou Tang
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
| | - Yang Liu
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
| | - Yichi Sun
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
| | - Yu Xiong
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
| | - Yan Gu
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, China
| | - Jing Zhou
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
- *Correspondence: Jing Zhou, ; Yan Ouyang, ; Shichao Zhang,
| | - Yan Ouyang
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, Guizhou Medical University, Guiyang, China
- *Correspondence: Jing Zhou, ; Yan Ouyang, ; Shichao Zhang,
| | - Shichao Zhang
- Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, China
- *Correspondence: Jing Zhou, ; Yan Ouyang, ; Shichao Zhang,
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19
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Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives. Cancers (Basel) 2022; 14:cancers14225545. [PMID: 36428637 PMCID: PMC9688479 DOI: 10.3390/cancers14225545] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/15/2022] Open
Abstract
Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.
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20
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Role of Different Types of miRNAs in Some Cardiovascular Diseases and Therapy-Based miRNA Strategies: A Mini Review. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2738119. [PMID: 36187500 PMCID: PMC9519277 DOI: 10.1155/2022/2738119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/26/2022] [Accepted: 08/27/2022] [Indexed: 11/17/2022]
Abstract
The role of microRNAs (miRNAs) in the pathogenesis of cardiovascular disease has been extensively studied. miRNAs have been highlighted as an important physiological regulator for activities like cardiac protection. miRNAs are present in the circulation, and they have been investigated as physiological markers, especially in the condition of heart failure. However, there is less compelling verification that miRNAs can outperform traditional biomarkers. However, clinical evidence is still required. In this review article, we explored the feasibility of miRNAs as diagnostic biomarkers for heart failure in a systematic study. Searching in the PubMed database to identify miRNA molecules that are differentially expressed between groups of patients with heart failure or heart disease and controls, throughout the investigation, we discovered no significant overlap in differentially expressed miRNAs. Only four miRNAs (“miR-126,” “miR-150-5p,” “hsa-miR-233,” and “miR-423-5p”) were differentially expressed. Results from our review show that there is not enough evidence to support the use of miRNAs as biomarkers in clinical settings.
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21
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Abstract
ABSTRACT Preoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.
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22
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Tang T, Yu S, Song Z, Pan X, Xu F, Wu Y, Zhang L. Comprehensive Analysis of miRNA-Mediated Regulatory Network and Identification of Prognosis Biomarkers in Rectal Cancer. Front Genet 2022; 13:792984. [PMID: 35495167 PMCID: PMC9039402 DOI: 10.3389/fgene.2022.792984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/31/2022] [Indexed: 01/05/2023] Open
Abstract
Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.
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Affiliation(s)
- Tingting Tang
- Department of Pathology, Ruian People’s Hospital, Zhejiang, China
| | - Sisi Yu
- Department of Pathology, Ruian People’s Hospital, Zhejiang, China
| | - Zekai Song
- Department of Pathology, Ruian People’s Hospital, Zhejiang, China
| | - Xiaofu Pan
- Department of Laboratory Medicine, Ruian People’s Hospital, Zhejiang, China
| | - Fang Xu
- Department of Digestive System, Ruian People’s Hospital, Zhejiang, China
| | - Yanke Wu
- Department of Pathology, Ruian People’s Hospital, Zhejiang, China
| | - Liang Zhang
- Department of Pathology, Ruian People’s Hospital, Zhejiang, China
- *Correspondence: Liang Zhang,
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23
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Mukherjee S, Shelar B, Krishna S. Versatile role of miR-24/24-1*/24-2* expression in cancer and other human diseases. Am J Transl Res 2022; 14:20-54. [PMID: 35173828 PMCID: PMC8829624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 10/08/2021] [Indexed: 06/14/2023]
Abstract
MiRNAs (miRs) have been proven to be well-validated therapeutic targets. Emerging evidence has demonstrated that intricate, intrinsic and paradoxical functions of miRs are context-dependent because of their multiple upstream regulators, broad spectrum of downstream molecular targets and distinct expression in various tissues, organs and disease states. Targeted therapy has become an emerging field of research. One key for the development of successful miR-based/targeted therapy is to acquire integrated knowledge of its regulatory network and its association with disease phenotypes to identify critical nodes of the underlying pathogenesis. Herein, we systematically summarized the comprehensive role of miR-24-3p (miR-24), along with its passenger strands miR-24-1-5p* (miR-24-1) and miR-24-2-5p* (miR-24-2), emphasizing their microenvironment, intracellular targets, and associated gene networks and regulatory phenotypes in 18 different cancer types and 13 types of other disorders. MiR-24 targets and regulates numerous genes in various cancer types and enhances the expression of several oncogenes (e.g., cMyc, BCL2 and HIF1), which are challenging in terms of druggability. In contrast, several tumor suppressor proteins (p21 and p53) have been reported to be downregulated by miR-24. MiR-24 also regulates the cell cycle and is associated with numerous cancer hallmarks such as apoptosis, proliferation, metastasis, invasion, angiogenesis, autophagy, drug resistance and other diseases pathogenesis. Overall, miR-24 plays an emerging role in the diagnosis, prognosis and pathobiology of various diseases. MiR-24 is a potential target for targeted therapy in the era of precision medicine, which expands the landscape of targetable macromolecules, including undruggable proteins.
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Affiliation(s)
| | | | - Sudhir Krishna
- National Centre for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR)Bellary Road, Bangalore 560065, Karnataka, India
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24
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Dougherty U, Mustafi R, Zhu H, Zhu X, Deb D, Meredith SC, Ayaloglu-Butun F, Fletcher M, Sanchez A, Pekow J, Deng Z, Amini N, Konda VJ, Rao VL, Sakuraba A, Kwesi A, Kupfer SS, Fichera A, Joseph L, Hart J, He F, He TC, West-Szymanski D, Li YC, Bissonnette M. Upregulation of polycistronic microRNA-143 and microRNA-145 in colonocytes suppresses colitis and inflammation-associated colon cancer. Epigenetics 2021; 16:1317-1334. [PMID: 33356812 PMCID: PMC8813074 DOI: 10.1080/15592294.2020.1863117] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 11/08/2020] [Accepted: 12/07/2020] [Indexed: 12/25/2022] Open
Abstract
Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3'UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, -148a or -152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3'UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.
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Affiliation(s)
| | - Reba Mustafi
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Hongyan Zhu
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Xiaorong Zhu
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Dilip Deb
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | | | | | - Arantxa Sanchez
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Joel Pekow
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Zifeng Deng
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Nader Amini
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Vani J Konda
- Department of Medicine, Baylor University, Dallas, TX, USA
| | - Vijaya L. Rao
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | - Akushika Kwesi
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Sonia S Kupfer
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | - Loren Joseph
- Departments of Pathology, Beth Israel, Harvard Medical School, Boston, MA, USA
| | - John Hart
- Departments of Pathology, University of Chicago, Chicago IL, USA
| | - Fang He
- Departments of Orthopedics, The University of Chicago, Chicago, IL, USA
| | - Tong-Chuan He
- Departments of Orthopedics, The University of Chicago, Chicago, IL, USA
| | | | - Yan Chun Li
- Department of Medicine, University of Chicago, Chicago IL, USA
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25
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Lu YH, Huang ZY. Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. Mol Med 2021; 27:148. [PMID: 34781898 PMCID: PMC8591874 DOI: 10.1186/s10020-021-00395-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/07/2021] [Indexed: 01/03/2023] Open
Abstract
Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped according to their sensitivity to IM as the responder group (N = 66) and the non-responder group (N = 42). Real-time quantitative PCR (RT-qPCR) was performed to evaluate the expression of candidate circular RNAs (circRNAs), microRNA (miRNAs) and messenger RNA (mRNAs). No significant difference was noted regarding demographic and clinicopathological characteristics between the responder group and the non-responder group. The expression of circ_0080145, circ_0051886 and ABL1 mRNA was significantly increased, while the expression of miR-203 and miR-637 was decreased in the non-responder group as compared with the responders. By using in-silicon analysis, it was predicted that circ_0080145 and circ_0051886 targeted miR-203 and miR-637 respectively, and ABL1 was found to be shared direct target gene of miR-203 and miR-637. Ectopic over-expression of circ_0080145 and circ_0051886 respectively reduced the expression of miR-203 and miR-637. The expression of ABL1 mRNA/protein was most upregulated in culture cells co-transfected with circ_0080145 and circ_0051886 as compared with those cells individually transfected. This study established the signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. The deregulation of circ_0080145 and circ_0051886 is, at least partially, responsible for the development of IM chemoresistance in CML by regulating expression of ABL1 via modulating expression of miR-203 and miR-637.
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Affiliation(s)
- Yao-Hua Lu
- Department of Pharmacy, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, China.
| | - Zhong-Yi Huang
- Department of Pharmacy, Jing'an District Central Hospital, No 259 Xikang Road, Jing'an District, Shanghai, 200040, China.
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26
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Moazzendizaji S, Sevbitov A, Ezzatifar F, Jalili HR, Aalii M, Hemmatzadeh M, Aslani S, Gholizadeh Navashenaq J, Safari R, Hosseinzadeh R, Rahmany MR, Mohammadi H. microRNAs: Small molecules with a large impact on colorectal cancer. Biotechnol Appl Biochem 2021; 69:1893-1908. [PMID: 34550619 DOI: 10.1002/bab.2255] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/03/2021] [Indexed: 12/23/2022]
Abstract
Colorectal cancer (CRC) accounts for one of the main cancer-related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF-β pathways, was clarified.
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Affiliation(s)
- Sahand Moazzendizaji
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Andrey Sevbitov
- Head of Department of Propaedeutics of Dental Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Fatemeh Ezzatifar
- Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hamid Reza Jalili
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Morteza Aalii
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Maryam Hemmatzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Roghaiyeh Safari
- Molecular and Cellular Epigenetics (GIGA), University of Liege, Sart-Tilman Liège, Belgium.,13. Molecular and Cellular Biology (TERRA), Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium
| | - Ramin Hosseinzadeh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Rahmany
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
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27
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Cervena K, Novosadova V, Pardini B, Naccarati A, Opattova A, Horak J, Vodenkova S, Buchler T, Skrobanek P, Levy M, Vodicka P, Vymetalkova V. Analysis of MicroRNA Expression Changes During the Course of Therapy In Rectal Cancer Patients. Front Oncol 2021; 11:702258. [PMID: 34540669 PMCID: PMC8444897 DOI: 10.3389/fonc.2021.702258] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/16/2021] [Indexed: 12/28/2022] Open
Abstract
MicroRNAs (miRNAs) regulate gene expression in a tissue-specific manner. However, little is known about the miRNA expression changes induced by the therapy in rectal cancer (RC) patients. We evaluated miRNA expression levels before and after therapy and identified specific miRNA signatures reflecting disease course and treatment responses of RC patients. First, miRNA expression levels were assessed by next-generation sequencing in two plasma samplings (at the time of diagnosis and a year after) from 20 RC patients. MiR-122-5p and miR-142-5p were classified for subsequent validation in plasma and plasma extracellular vesicles (EVs) on an independent group of RC patients (n=107). Due to the intrinsic high differences in miRNA expression levels between samplings, cancer-free individuals (n=51) were included in the validation phase to determine the baseline expression levels of the selected miRNAs. Expression levels of these miRNAs were significantly different between RC patients and controls (for all p <0.001). A year after diagnosis, miRNA expression profiles were significantly modified in patients responding to treatment and were no longer different from those measured in cancer-free individuals. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling (miR-122-5p: plasma: p=0.05, EVs: p=0.007; miR-142-5p: plasma: p=0.008). Besides, overexpression of miR-122-5p and miR-142-5p in RC cell lines inhibited cell growth and survival. This study provides novel evidence that circulating miR-122-5p and miR-142-5p have a high potential for RC screening and early detection as well as for the assessment of patients' outcomes and the effectiveness of treatment schedule.
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Affiliation(s)
- Klara Cervena
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia
| | - Vendula Novosadova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Prague, Czechia
| | - Barbara Pardini
- Molecular Genetics Epidemiology Unit, Italian Institute for Genomic Medicine, c/o IRCCS Candiolo,, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Alessio Naccarati
- Molecular Genetics Epidemiology Unit, Italian Institute for Genomic Medicine, c/o IRCCS Candiolo,, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Alena Opattova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Josef Horak
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Sona Vodenkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Tomas Buchler
- Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Pavel Skrobanek
- Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Miroslav Levy
- Department of Surgery, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
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28
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Kiss D, Machackova T, Souckova K, Fabian P, Krepelkova I, Svoboda M, Kiss I. An Independent Validation Study of Candidate microRNAs as Predictive Biomarkers for Bevacizumab-based Therapy in Patients With Metastatic Colorectal Cancer. In Vivo 2021; 35:2809-2814. [PMID: 34410972 DOI: 10.21873/invivo.12567] [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: 04/08/2021] [Revised: 06/04/2021] [Accepted: 06/11/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM The monoclonal antibody bevacizumab is a standard drug used in combination with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) based chemotherapy in the first or second-line treatment of metastatic colorectal cancer (mCRC). Our previous study identified and subsequently validated 4 microRNAs in a small group of patients as predictors of the therapeutic response to bevacizumab combined with chemotherapy. The aim of this follow-up study is to confirm the predictive ability of these tissue miRNAs in a larger independent cohort of mCRC patients. PATIENTS AND METHODS The retrospective study included 92 patients with generalized-radically inoperable tumors treated with the combined therapy of bevacizumab/FOLFOX in a standard regimen. RESULTS Expression levels of candidate miRNA biomarkers (miR-92b-3p, miR-3156-5p, miR-10a-5p and miR-125a-5p) were determined in tumor tissue specimens and statistically evaluated. MiR-92b-3p and miR-125a-5p were confirmed to be associated with radiological response according to RECIST criteria (p=0.005 and 0.05, respectively) and to be up-regulated in responders to bevacizumab/FOLFOX therapy. Higher levels of miR-92b-3p were also significantly associated with extended progression-free survival (p=0.024). CONCLUSION We have successfully confirmed miR-92b-3p to be up-regulated in tumor tissue of mCRC patients with good response to bevacizumab/FOLFOX therapy.
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Affiliation(s)
- David Kiss
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.,Department of Cardiology and Internal Medicine, University Hospital Brno, Brno, Czech Republic
| | - Tana Machackova
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Kamila Souckova
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Pavel Fabian
- Department of Clinical and Experimental Pahology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | | | - Marek Svoboda
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Igor Kiss
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic; .,Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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29
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Wang ZY, Li DL, Tian X, Zhang CY. A copper-free and enzyme-free click chemistry-mediated single quantum dot nanosensor for accurate detection of microRNAs in cancer cells and tissues. Chem Sci 2021; 12:10426-10435. [PMID: 34447534 PMCID: PMC8356811 DOI: 10.1039/d1sc01865e] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 07/06/2021] [Indexed: 12/31/2022] Open
Abstract
MicroRNAs (miRNAs) play key roles in the post-transcriptional regulation of genes, and their aberrant expression may disturb the normal gene regulation network to induce various diseases, and thus accurate detection of miRNAs is essential to early clinical diagnosis. Herein, we develop for the first time a single-quantum dot (QD)-based Förster resonance energy transfer (FRET) nanosensor to accurately detect miRNAs based on copper-free and enzyme-free cycling click chemistry-mediated tricyclic ligase chain reaction (LCR) amplification. We design four DNA probes namely DNA probes 1-4, with DNA probes 1 and 3 being modified with azide (N3) and DNA probes 2 and 4 being modified with dibenzocyclooctyne (DBCO). When target miRNA is present, DNA probes 1 and 2 can proceed via copper-free and enzyme-free click chemistry to generate the probes 1-2 ligation product. Subsequently, DNA probes 3 and 4 can hybridize with the probes 1-2 ligation product to generate the probes 3-4 ligation product. Both the probes 1-2 ligation product and probes 3-4 ligation product can act as the templates to initiate cycling click chemistry-mediated tricyclic LCR amplification whose products can be easily measured by the single-QD-based FRET nanosensor. This assay does not involve any enzymatic reverse transcription, copper catalyst, and ligase enzyme, and it exhibits excellent selectivity, high sensitivity, and the capability of differentiating even single-base mismatches. Moreover, this nanosensor can accurately quantify miRNA-155 even at the single-cell level, and it can distinguish the miRNA-155 expression in tissues of healthy persons and nonsmall cell lung cancer (NSCLC) patients.
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Affiliation(s)
- Zi-Yue Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University Jinan 250014 China +86 0531-82615258 +86 0531-86186033
| | - Dong-Ling Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University Jinan 250014 China +86 0531-82615258 +86 0531-86186033
| | - Xiaorui Tian
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University Jinan 250014 China +86 0531-82615258 +86 0531-86186033
| | - Chun-Yang Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University Jinan 250014 China +86 0531-82615258 +86 0531-86186033
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30
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Khalighfard S, Kalhori MR, Amiriani T, Poorkhani A, Khori V, Esmati E, Lashkari M, Najafi A, Alizadeh AM. A systematic approach introduced novel targets in rectal cancer by considering miRNA/mRNA interactions in response to radiotherapy. Cancer Biomark 2021; 33:97-110. [PMID: 34366323 DOI: 10.3233/cbm-210079] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The discovery of miRNA/mRNA interactions in several biological samples prompted the researchers to explore new biomarkers in tumors. OBJECTIVE We aimed to investigate the interactions of miRNA/mRNA in response to radiotherapy in the plasma samples of rectal cancer patients. METHODS Five microarray datasets related to cancerous and non-cancerous individuals were first used to construct networks. The databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze pathway enrichment. The plasma samples were then collected from 55 patients with recently diagnosed rectal cancer and 10 healthy subjects. For radiotherapy courses, the patients have consecutively received 30 sessions of local radiation for six weeks. At last, the expression of selected genes and miRNAs was experimentally measured before and after radiotherapy by qPCR, and the protein levels of the target genes were measured by ELISA assay. We evaluated the therapeutic responses based on the tumor regression grade of the Dworak classification. RESULTS We identified 5 up-regulated and 5 down-regulated miRNAs and 8 up-regulated and 3 down-regulated genes of the databases. There was a significant increase in tumor suppressor miRNAs, including miR-101-3p, miR-145-5p, miR-26a-5p, miR-34a-5p, and a significant decrease in oncomiRs, including miR-221-3p and miR-17-5p, after radiotherapy compared to the pre-treatment. Moreover, the up-regulated miR-17-5p and miR-221-5p and the down-regulated miR-101-3p and miR-145-5p were directly related to rectal cancer through the interaction with the Wnt, RAS, PI3K, and TGF-β signaling pathways. An analysis of receiver operating characteristics showed that miRNAs 221, 17, and 23 were response-related in locally advanced rectal cancer patients. CONCLUSIONS It seems that monitoring the miRNA/mRNA interactions during radiotherapy can be an appropriate diagnostic tool to track the recovery process and respond to standard therapies.
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Affiliation(s)
- Solmaz Khalighfard
- Radiation Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Taghi Amiriani
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Amirhoushang Poorkhani
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Vahid Khori
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ebrahim Esmati
- Radiation Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Marzieh Lashkari
- Radiation Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Najafi
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Radiation Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Mohammad Alizadeh
- Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Radiation Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Beklen H, Yildirim E, Kori M, Turanli B, Arga KY. Systems-level biomarkers identification and drug repositioning in colorectal cancer. World J Gastrointest Oncol 2021. [DOI: 10.4251/wjgo.v13.i7.463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Beklen H, Yildirim E, Kori M, Turanli B, Arga KY. Systems-level biomarkers identification and drug repositioning in colorectal cancer. World J Gastrointest Oncol 2021; 13:638-661. [PMID: 34322194 PMCID: PMC8299930 DOI: 10.4251/wjgo.v13.i7.638] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the most commonly diagnosed fatal cancer in both women and men worldwide. CRC ranked second in mortality and third in incidence in 2020. It is difficult to diagnose CRC at an early stage as there are no clinical symptoms. Despite advances in molecular biology, only a limited number of biomarkers have been translated into routine clinical practice to predict risk, prognosis and response to treatment. In the last decades, systems biology approaches at the omics level have gained importance. Over the years, several biomarkers for CRC have been discovered in terms of disease diagnosis and prognosis. On the other hand, a few drugs are being developed and used in clinics for the treatment of CRC. However, the development of new drugs is very costly and time-consuming as the research and development takes about 10 years and more than $1 billion. Therefore, drug repositioning (DR) could save time and money by establishing new indications for existing drugs. In this review, we aim to provide an overview of biomarkers for the diagnosis and prognosis of CRC from the systems biology perspective and insights into DR approaches for the prevention or treatment of CRC.
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Affiliation(s)
- Hande Beklen
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Esra Yildirim
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Medi Kori
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Beste Turanli
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Kazim Yalcin Arga
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
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Zhou M, Xu Q, Huang D, Luo L. Regulation of gene transcription of B lymphoma Mo-MLV insertion region 1 homolog (Review). Biomed Rep 2021; 14:52. [PMID: 33884195 PMCID: PMC8056379 DOI: 10.3892/br.2021.1428] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 02/19/2021] [Indexed: 12/18/2022] Open
Abstract
B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is a core protein component of the polycomb repressive complex 1 that inhibits cell senescence and maintains the self-renewal ability of stem cells via downregulation of p16Ink4a and p19Arf expression. Bmi-1 serves an important role in hematopoietic stem cell maintenance and neurodevelopment during embryonic development, and it has been shown to enhance tumorigenesis by promoting cancer stem cell self-renewal and epithelial to mesenchymal transition. Emerging evidence suggests that Bmi-1 overexpression is closely related to the development and progression of various types of cancer, and that downregulation of Bmi-1 expression can inhibit the proliferation, invasion and metastasis of cancer cells. It is therefore important to elucidate the mechanisms underlying the regulation of Bmi-1 expression both under normal growth conditions and in malignant tissues. In the present review, the current body of knowledge pertaining to the transcriptional and post-transcriptional regulation of the BMI-1 gene is discussed, and the potential mechanisms by which Bmi-1 is dysregulated in various types of cancer are highlighted. Bmi-1 expression is primarily controlled via transcriptional regulation, and is regulated by the transcription https://www.ushuaia.pl/hyphen/?ln=en factors of the Myc family, including Myb, Twist1, SALL4 and E2F-1. Post-transcriptionally, regulation of Bmi-1 expression is inhibited by several microRNAs and certain small-molecule drugs. Thus, regulatory transcriptional factors are potential therapeutic targets to reduce Bmi-1 expression in cancer cells. Thus, the present review provides an up-to-date review on the regulation of BMI-1 gene expression at the transcriptional and post-transcriptional level.
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Affiliation(s)
- Meizhen Zhou
- Department of Gastroenterology, Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qichao Xu
- Department of Gastroenterology, Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Deqiang Huang
- Department of Gastroenterology, Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Lingyu Luo
- Department of Gastroenterology, Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Wang N, Xu Y, Guo Q, Zhu C, Zhao W, Qian W, Zheng M. Effects of miR-132-3p on progress and epithelial mesenchymal transition of non-small cell lung cancer via regulating KLF7. J Thorac Dis 2021; 13:2426-2436. [PMID: 34012590 PMCID: PMC8107552 DOI: 10.21037/jtd-21-353] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background MicroRNAs (miRNAs) often appear as oncogenes or tumor suppressor genes. The aim of this research was to examine miR-132-3p and Kruppel-like factor 7 (KLF7) effects in the development of non-small cell lung cancer (NSCLC). Methods We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine miR-132-3p expression in tissue specimens and 6 cells (A549, H1650, H292, H1299, H1944, BEAS-2b). Luciferase report forecasted the targeting relationship between miR-132-3p and KLF7. The expression of KLF7 and interstitial protein was determined by western blot. Proliferation test and Transwell assay were adopted for examining cell development. The Cell Counting Kit-8 (CCK-8) colorimetric method was used to observe the effects of miR-132-3p and KLF7 on the proliferation, metastasis, and invasion of NSCLC tumor cells. In order to determine whether the metastasis of NSCLC tumor cells was epithelial-mesenchymal transition (EMT)-mediated, supplementary experiments with E-cadherin and vimentin were performed. Results An increased expression of miR-132-3p was detected in NSCLC. Its mimic promoted the proliferation of tumor cells. As an immediate site of miR-132-3p, KLF7 was reversely adjusted via miR-132-3p and restrained the development of tumor cells in NSCLC, the effects of which were attenuated via KLF7 over-expression. Besides, the presence of EMT-related diversions was confirmed in NSCLC. Conclusions By targeting KLF7, miR-132-3p was capable of promoting the proceeding of NSCLC tumor cells. We discovered miR-132-3p/KLF7 route may exhibit curative target for NSCLC.
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Affiliation(s)
- Ning Wang
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ye Xu
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingkui Guo
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Zhu
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen Zhao
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenliang Qian
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Zheng
- Thoracic Surgery Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Grady WM. Epigenetic alterations in the gastrointestinal tract: Current and emerging use for biomarkers of cancer. Adv Cancer Res 2021; 151:425-468. [PMID: 34148620 DOI: 10.1016/bs.acr.2021.02.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer is a leading cause of cancer related deaths worldwide. One of the hallmarks of cancer and a fundamental trait of virtually all gastrointestinal cancers is genomic and epigenomic DNA alterations. Cancer cells acquire genetic and epigenetic alterations that drive the initiation and progression of the cancers by altering the molecular and cell biological process of the cells. These alterations, as well as other host and microenvironment factors, ultimately mediate the initiation and progression of cancers, including colorectal cancer. Epigenetic alterations, which include changes affecting DNA methylation, histone modifications, chromatin structure, and noncoding RNA expression, have emerged as a major class of molecular alteration in colon polyps and colorectal cancer. The classes of epigenetic alterations, their status in colorectal polyps and cancer, their effects on neoplasm biology, and their application to clinical care will be discussed.
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Affiliation(s)
- William M Grady
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA, United States.
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He L, Chang H, Qi Y, Zhang B, Shao Q. ceRNA Networks: The Backbone Role in Neoadjuvant Chemoradiotherapy Resistance/Sensitivity of Locally Advanced Rectal Cancer. Technol Cancer Res Treat 2021; 20:15330338211062313. [PMID: 34908512 PMCID: PMC8689620 DOI: 10.1177/15330338211062313] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/21/2021] [Accepted: 11/02/2021] [Indexed: 11/30/2022] Open
Abstract
Approximately 40% of rectal cancers during initial diagnosis are identified as locally advanced rectal cancers (LARCs), for which the standardized treatment scenario is total mesorectal excision following neoadjuvant chemoradiotherapy (nCRT). nCRT can lead to discernible reductions in local relapse rate and distant metastasis rate in LARC patients, in whom previously inoperable tumors may potentially be surgically removed. However, only 4% to 20% cases can attain pathological complete response, and the remaining patients who are unresponsive to nCRT have to suffer from the side effects plus toxicities and may encounter poor survival outcomes due to the late surgical intervention. As such, employing potential biomarkers to differentiate responders from nonresponders before nCRT implementation appears to be the overarching goal. Well-defined competing endogenous RNA (ceRNA) networks include long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA and circRNA-miRNA-mRNA networks. As ceRNAs, lncRNAs, and circRNAs sponge miRNAs to indirectly suppress miRNAs downstream of oncogenic mRNAs or tumor-suppressive mRNAs. The abnormal expression of mRNAs regulates the nCRT-induced DNA damage repair process through pluralistic carcinogenic signaling pathways, thereby bringing about alterations in the nCRT resistance/sensitivity of tumors. Moreover, many molecular mechanisms relevant to cell proliferation, metastasis, or apoptosis of cancers (eg, epithelial-mesenchymal transition and caspase-9-caspase-3 pathway) are influenced by ceRNA networks. Herein, we reviewed a large group of abnormally expressed mRNAs and noncoding RNAs that are associated with nCRT resistance/sensitivity in LARC patients and ultimately pinpointed the backbone role of ceRNA networks in the molecular mechanisms of nCRT resistance/sensitivity.
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Affiliation(s)
- Lin He
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, China
| | - Hao Chang
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
| | - Yuhong Qi
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
| | - Bing Zhang
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
| | - Qiuju Shao
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, China
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Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer. Mol Ther 2020; 29:587-596. [PMID: 33333293 DOI: 10.1016/j.ymthe.2020.12.017] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/15/2020] [Accepted: 12/09/2020] [Indexed: 12/18/2022] Open
Abstract
The therapeutic strategies of stage II/III colorectal cancer (CRC) patients after curative surgery remain controversial. In the clinical decision-making process, oncologists need to answer questions such as whether adjuvant chemotherapy is necessary or which therapeutic regimen should be given to each patient. At present, whether adjuvant chemotherapy should be applied is primarily based on histopathological features and clinical risk factors. However, only a fraction of patients can benefit from it. More rigorous stratifying biomarkers are urgently needed to help further distinguishing these populations of patients. Recent progress in next-generation sequencing and high-throughput technologies has greatly promoted biomarker discovery as well as our understanding of the underlying mechanisms in CRC. Novel genetic and epigenetic biomarkers that are associated with prognosis or therapeutic responses have emerged. In this review, we discuss the strategies of biomarker discovery and summarize the status and assess the utility of previously published biomarkers in CRC.
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Dalal N, Jalandra R, Sharma M, Prakash H, Makharia GK, Solanki PR, Singh R, Kumar A. Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives. Biomed Pharmacother 2020; 131:110648. [PMID: 33152902 DOI: 10.1016/j.biopha.2020.110648] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/09/2020] [Accepted: 08/16/2020] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) ranks third among the most commonly occurring cancers worldwide, and it causes half a million deaths annually. Alongside mechanistic study for CRC detection and treatment by conventional techniques, new technologies have been developed to study CRC. These technologies include genomics, transcriptomics, proteomics, and metabolomics which elucidate DNA markers, RNA transcripts, protein and, metabolites produced inside the colon and rectum part of the gut. All these approaches form the omics arena, which presents a remarkable opportunity for the discovery of novel prognostic, diagnostic and therapeutic biomarkers and also delineate the underlying mechanism of CRC causation, which may further help in devising treatment strategies. This review also mentions the latest developments in metagenomics and culturomics as emerging evidence suggests that metagenomics of gut microbiota has profound implications in the causation, prognosis, and treatment of CRC. A majority of bacteria cannot be studied as they remain unculturable, so culturomics has also been strengthened to develop culture conditions suitable for the growth of unculturable bacteria and identify unknown bacteria. The overall purpose of this review is to succinctly evaluate the application of omics technologies in colorectal cancer research for improving the diagnosis and treatment strategies.
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Affiliation(s)
- Nishu Dalal
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India; Department of Environmental Science, Satyawati College, Delhi University, Delhi 110052, India
| | - Rekha Jalandra
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India; Department of Zoology, Maharshi Dayanand University, Rohtak 124001, India
| | - Minakshi Sharma
- Department of Zoology, Maharshi Dayanand University, Rohtak 124001, India
| | - Hridayesh Prakash
- Amity Institute of Virology and Immunology, Amity University, Sector 125, Noida 201313, Uttar Pradesh, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Pratima R Solanki
- Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi 110067, India
| | - Rajeev Singh
- Department of Environmental Science, Satyawati College, Delhi University, Delhi 110052, India.
| | - Anil Kumar
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India.
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Nandini DB, Rao RS, Deepak BS, Reddy PB. Sulforaphane in broccoli: The green chemoprevention!! Role in cancer prevention and therapy. J Oral Maxillofac Pathol 2020; 24:405. [PMID: 33456268 PMCID: PMC7802872 DOI: 10.4103/jomfp.jomfp_126_19] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 09/06/2019] [Accepted: 03/05/2020] [Indexed: 02/06/2023] Open
Abstract
Isothicyanates present in cruciferous vegetables are known to exhibit chemoprevention by various mechanisms. Presently, there is growing evidence that a phytochemical compound known as sulforaphane in these green leafy vegetables is found to be effective in preventing and treating various cancers such as prostate cancer, breast cancer, colon cancer, skin, urinary bladder and oral cancers. This component is naturally present in the broccoli sprouts, kale, cabbage, cauliflower and garden cress and is available as a commercial supplementary pill called Broccoli extract. Availability of many bioactive substances such as vitamins, polyphenols, sulfides, glucosinolates and antioxidants makes broccoli consumption important in daily diet regularly. Researchers have named it as "Green chemoprevention." It is easily affordable and more cost-effective than the traditional chemopreventive drugs. Results from the epidemiological and experimental studies have emphasized the role of sulforophane as a complementary or alternative chemopreventive agent.
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Affiliation(s)
- D B Nandini
- Department of Oral Pathology and Microbiology, Dental College, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Roopa S Rao
- Department of Oral Pathology and Microbiology, M. S. Ramaiah Dental College, Bengaluru, Karnataka, India
| | - B S Deepak
- Department of Conservative Dentistry, Dental College, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Praveen B Reddy
- Department of Oral and Maxillofacial Surgery, Dental College, Regional Institute of Medical Sciences, Imphal, Manipur, India
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Mei H, Wen Y. MicroRNAs for Diagnosis and Treatment of Colorectal Cancer. Endocr Metab Immune Disord Drug Targets 2020; 21:47-55. [PMID: 32819240 DOI: 10.2174/1871530320999200818134339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 05/28/2020] [Accepted: 07/15/2020] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease- free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRC diagnosis and treatment.
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Affiliation(s)
- Haitao Mei
- Shanghai General Hospital, Department of general surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yugang Wen
- Shanghai General Hospital, Department of general surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Imedio L, Cristóbal I, Rubio J, Santos A, Rojo F, García-Foncillas J. MicroRNAs in Rectal Cancer: Functional Significance and Promising Therapeutic Value. Cancers (Basel) 2020; 12:E2040. [PMID: 32722203 PMCID: PMC7464102 DOI: 10.3390/cancers12082040] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/19/2020] [Accepted: 07/22/2020] [Indexed: 12/24/2022] Open
Abstract
It is well-known that microRNAs (miRNAs) are critical mediators of initiation and disease progression in many human cancers. Rectal cancer is a highly prevalent tumor, accounting for around one third of newly diagnosed colorectal cancers. The usefulness of miRNAs as clinical biomarkers predictive of the outcome and response to chemoradiotherapy has been well-reported for rectal cancer. However, the existing literature on their functional and therapeutic impact needs to be put in context to clarify their role in disease pathogenesis. Therfore, this review is focused on the functional relevance of miRNAs as key regulators of signaling pathways in rectal cancer and their potential therapeutic value as novel molecular targets in this disease.
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Affiliation(s)
- Laura Imedio
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (L.I.); (J.R.); (A.S.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-Universidad Autonoma de Madrid (UAM), E-28040 Madrid, Spain
| | - Ion Cristóbal
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (L.I.); (J.R.); (A.S.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-Universidad Autonoma de Madrid (UAM), E-28040 Madrid, Spain
| | - Jaime Rubio
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (L.I.); (J.R.); (A.S.)
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
| | - Andrea Santos
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (L.I.); (J.R.); (A.S.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-Universidad Autonoma de Madrid (UAM), E-28040 Madrid, Spain
| | - Federico Rojo
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain;
| | - Jesús García-Foncillas
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (L.I.); (J.R.); (A.S.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-Universidad Autonoma de Madrid (UAM), E-28040 Madrid, Spain
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
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Tian QQ, Xia J, Zhang X, Gao BQ, Wang W. miR-331-3p Inhibits Tumor Cell Proliferation, Metastasis, Invasion by Targeting MLLT10 in Non-Small Cell Lung Cancer. Cancer Manag Res 2020; 12:5749-5758. [PMID: 32765078 PMCID: PMC7368563 DOI: 10.2147/cmar.s249686] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/24/2020] [Indexed: 12/18/2022] Open
Abstract
Objective Mounting research has established the role of microRNAs (miRNAs) as oncogenes or anti-oncogenes (tumor suppressors) in the development and progression of several cancers. The purpose of our current study is to delineate the roles and functional mechanisms of miR-331-3p and MLLT10 in non-small cell lung cancer (NSCLC) tumorigenesis. Patients and Methods Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was employed to measure miR-331-3p expression levels in twenty-six matched tumor tissues and non-cancerous tissues collected from patients suffering from NSCLC, and from six NSCLC cell lines separately: A549, H1650, H292, H1299, H1944 and BEAS-2b. We employed the dual-luciferase activity assay to check whether the putative gene, MLLT10, was a downstream target of miR-331-3p in NSCLC pathogenesis and development. Western blot was conducted to analyze the protein expression levels of MLLT10 (AF10), E-cadherin, Vimentin, and GAPDH. CCK-8 assay, transwell migration assay, and transwell invasion assay were carried out to observe the functions of miR-331-3p and MLLT10 on NSCLC tumor cell proliferation, metastasis, and invasion, respectively. To identify whether the metastasis of NSCLC tumor cells was EMT-mediated, supplementary experiments involving E-cadherin and Vimentin were implemented. Results miR-331-3p was downregulated in NSCLC, which promoted tumor cell proliferation, whereas the overexpression of miR-331-3p inhibited tumor cell proliferation. Being a direct target of miR-331-3p, MLLT10 was negatively modulated by miR-331-3p, which suppressed tumor cell proliferation, migration, and invasion in NSCLC. However, MLLT10 overexpression alleviated the above inhibitory effects. Furthermore, EMT-mediated metastasis was proved to be present in NSCLC. Conclusion miR-331-3p played a suppressor role in NSCLC tumor cell proliferation, EMT-mediated metastasis, and invasion by targeting MLLT10. Our findings highlighted that miR-331-3p/MLLT10 axis could be useful as a clinical diagnostic marker and therapeutic target in NSCLC patients.
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Affiliation(s)
- Qing-Qing Tian
- Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Jing Xia
- General Department of Houhu, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xin Zhang
- Department of Radiology, The Fourth People's Hospital of Huai'an, Huai'an, Huai'an, People's Republic of China
| | - Bao-Qin Gao
- Operating Room, Huai'an Second People's Hospital and the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, People's Republic of China
| | - Wei Wang
- Department of Oncology, Huai'an Second People's Hospital and the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, People's Republic of China
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Heydari Z, Rahaie M, Alizadeh AM, Agah S, Khalighfard S, Bahmani S. Effects of Lactobacillus acidophilus and Bifidobacterium bifidum Probiotics on the Expression of MicroRNAs 135b, 26b, 18a and 155, and Their Involving Genes in Mice Colon Cancer. Probiotics Antimicrob Proteins 2020; 11:1155-1162. [PMID: 30311185 DOI: 10.1007/s12602-018-9478-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
A wide range of sources supports that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. In this case, it seems that the probiotics may have a possible molecular mechanism via microRNAs (miRNAs). The present study is aimed to evaluate the effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of miRNAs 135b, 26b, 18a, and 155 and their target genes, including APC, PTEN, KRAS, and PU.1 in mouse azoxymethane (AOM)-induced colon cancer. Thirty-eight male BALB/c mice were randomly divided into four groups: the control, AOM, Lactobacillus acidophilus, and Bifidobacterium bifidum to deliberate the effects of the probiotics on the miRNAs and their target genes. Except for the control group, the rest groups were weekly given AOM (15 mg/kg, s.c) in three consecutive weeks to induce mouse colon cancer. The animals were given 1.5 g powders of L. acidophilus (1 × 109 cfu/g) and B. bifidum (1 × 109 cfu/g) in 30 cc drinking water in the related groups for 5 months. At the end of the study, the animals were sacrificed and their blood and colon samples were removed for the molecular analyses. The results showed that the expression of the miR-135b, miR-155, and KRAS was increased in the AOM group compared to the control group in both the plasma and the colon tissue samples, and the consumption of the probiotics decreased their expression. Moreover, the miR-26b, miR-18a, APC, PU.1, and PTEN expressions were decreased in the AOM group compared to the control group and the consumption of the probiotics increased their expressions. It seems that Lactobacillus acidophilus and Bifidobacterium bifidum though increasing the expression of the tumor suppressor miRNAs and their target genes and decreasing the oncogenes can improve colon cancer treatment.
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Affiliation(s)
- Zahra Heydari
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Mahdi Rahaie
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Ali Mohammad Alizadeh
- Cancer Research Center, Tehran University of Medical Sciences, Tehran, 1419733141, Iran.
- Cancer Biology Research Center, Tehran University of Medical Science, Tehran, Iran.
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Solmaz Khalighfard
- Cancer Research Center, Tehran University of Medical Sciences, Tehran, 1419733141, Iran
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Sahar Bahmani
- Research and Development Department, Zist Takhmir Company, Tehran, Iran
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44
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Liu C, Hou J, Shan F, Wang L, Lu H, Ren T. Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Cell Progression and Paclitaxel Resistance by Regulating miR-126-5p/ATAD2 Axis. Onco Targets Ther 2020; 13:4931-4942. [PMID: 32581554 PMCID: PMC7276211 DOI: 10.2147/ott.s237580] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 04/21/2020] [Indexed: 12/11/2022] Open
Abstract
Background Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) and microRNA-126-5p (miR-126-5p) were reported to be related to the development of colorectal carcinoma (CRC). However, the detailed mechanism of CRNDE and miR-126-5p is not fully understood. The purpose of this research was to explore their roles and molecular mechanism in CRC. Methods Quantitative real-time polymerase chain reaction was performed to detect the transcription levels of genes. Paclitaxel (PTX) was used to analyze cell drug resistance. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Furthermore, cell migratory and invasive abilities were measured using transwell assay. The interaction between miR-126-5p and CRNDE or ATPase family AAA domain-containing protein 2 (ATAD2) was predicted by online tool starbase and then confirmed using the dual-luciferase reporter assay. Besides, Western blot assay was carried out to detect the levels of proteins. Results CRNDE and ATAD2 expressions were upregulated and miR-126-5p expression was downregulated in CRC tissues and cells. CRNDE depletion repressed PTX resistance and the growth of CRC cells. Interestingly, we found that miR-126-5p was a target gene of CRNDE, and miR-126-5p directly targeted ATAD2. Furthermore, CRNDE affected CRC cell progression via modulation of miR-126-5p/ATAD2 axis in CRC cells. Conclusion Our data suggested that CRNDE regulated CRC cell development and PTX resistance by modulating miR-126-5p/ATAD2 axis, providing the theoretical basis for the treatment of CRC patients.
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Affiliation(s)
- Chang Liu
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
| | - Jianfeng Hou
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
| | - Fengxiao Shan
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
| | - Lijuan Wang
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
| | - Hanjie Lu
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
| | - Tiejun Ren
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People's Republic of China
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45
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Fu Q, Zhang J, Huang G, Zhang Y, Zhao M, Zhang Y, Xie J. microRNA-29b inhibits cell growth and promotes sensitivity to oxaliplatin in colon cancer by targeting FOLR1. Biofactors 2020; 46:136-145. [PMID: 31621972 DOI: 10.1002/biof.1579] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 09/25/2019] [Indexed: 12/18/2022]
Abstract
The present study was aimed to explore the functional role of microRNA (miR)-29b in colon cancer, as well as underlying mechanisms. Expressions of miR-29b and folate receptor 1 (FOLR1) were measured in both human colon tumor samples and cell lines. Colon cancer cell lines SW480 and SW620 were transfected with miR-29b mimic, antisense oligonucleotides (ASO)-miR-29b, small interfering (siRNA) against FOLR1 (si-FOLR1), or corresponding negative controls (NCs), and then were incubated with or without oxaliplatin (L-OHP). Thereafter, cell viability, cytotoxicity, cell apoptosis, and expression of FOLR1, ATP Binding Cassette Subfamily G Member 2 (ABCG2) and p-glycoprotein (p-gp) were analyzed. We found that miR-29b was significantly decreased, while FOLR1 was statistically elevated in colon cancer samples and cell lines compared to the nontumor samples and nontumourigenic immortalized human colon epithelial cell line FHC. Overexpression of miR-29b markedly inhibited cell viability, promoted sensitivity to L-OHP, stimulated cell apoptosis (all p < .05), and decreased the levels of ABCG2 and p-gp in cancer cells, whereas suppression of miR-29b showed contrary results. Moreover, we observed that FOLR1 was a direct target of miR-29b and was negatively regulated by miR-29b. In addition, the findings revealed that the effects of FOLR1 inhibition on cell viability, sensitivity to L-OHP, cell apoptosis, and the levels of ABCG2 and p-gp were similar to overexpression of miR-29b. Taken together, our study suggests that miR-29b inhibits cell growth and promotes sensitivity to L-OHP in colon cancer by targeting FOLR1.
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Affiliation(s)
- Qiang Fu
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jindai Zhang
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Gaofeng Huang
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yonglei Zhang
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Minghai Zhao
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yongchao Zhang
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jianguo Xie
- Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
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46
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Noorolyai S, Baghbani E, Aghebati Maleki L, Baghbanzadeh Kojabad A, Shanehbansdi D, Khaze Shahgoli V, Mokhtarzadeh A, Baradaran B. Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53. Adv Pharm Bull 2019; 10:130-134. [PMID: 32002372 PMCID: PMC6983996 DOI: 10.15171/apb.2020.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 08/04/2019] [Accepted: 08/13/2019] [Indexed: 12/18/2022] Open
Abstract
Purpose: Colorectal cancer (CRC) remains a universal and lethal cancer owing to metastatic and relapsing disease. Currently, the role of microRNAs has been checked in tumorigeneses. Numerous studies have revealed that between the tumor suppressor miRNAs, the reduced expression of miR-146a-5p and -193a-5p in several cancers including CRC tissues are related with tumor progression and poor prognosis of patients. The purpose of this study is to examine the role of miR-146 a-5p and -193 a-5p in CRC cell cycle progression.
Methods: The miR-193a-5p and -146 a-5p mimics were transfected into HT-29 CRC cells via jetPEI transfection reagent and their impact was assessed on p53, cyclin B, and NF-kB gene expression. The inhibitory effect of these miRNAs on cell cycle was assessed by flow cytometry. The consequence of miR-193a-5p and miR-146 a-5p on the protein expression level of Murine double minute 2 (MDM2) was assessed by western blotting.
Results: miR193a-5p and -146a-5p regulated the expression of MDM2 protein and p53, cyclin B, and NF-kB gene expression in CRC cells. Treatment of HT-29 cells with miRNA-146a-5p and -193a-5p induced G1 cell cycle arrest.
Conclusion: The findings of our study suggest that miR146a-5p and -193a-5p may act as a potential tumor suppressor by their influence on cell cycle progression in CRC cells. Thus, miRNA-146a-5p and -193a-5p restoration may be recommended as a potential therapeutic goal in the treatment of CRC patients.
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Affiliation(s)
- Saeed Noorolyai
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Baghbani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Introduction
| | | | | | | | | | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Soleimani A, Rahmani F, Saeedi N, Ghaffarian R, Khazaei M, Ferns GA, Avan A, Hassanian SM. The potential role of regulatory microRNAs of RAS/MAPK signaling pathway in the pathogenesis of colorectal cancer. J Cell Biochem 2019; 120:19245-19253. [PMID: 31512778 DOI: 10.1002/jcb.29268] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 06/11/2019] [Indexed: 12/17/2022]
Abstract
Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Dysregulation of RAS/MAPK signaling axis is frequently found in CRC patients. The RAS/MAPK axis regulates cancer cell proliferation, apoptosis, inflammation, migration, and metastasis. Oncogenic or tumor-suppressor microRNAs (miRNAs) for RAS/MAPK signaling play a key role in the pathogenesis of CRC and are considered as novel potential biomarkers for diagnosis and prognosis of human malignancies. This review summarizes the current knowledge of mechanisms of action of RAS/MAPK miRNAs in the development and progression of CRC for a better understanding and hence a better management of this disease.
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Affiliation(s)
- Atena Soleimani
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzad Rahmani
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nikoo Saeedi
- Student Research Committee, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Rana Ghaffarian
- Student Research Committee, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Brighton, Sussex, UK
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Fadaka AO, Klein A, Pretorius A. In silico identification of microRNAs as candidate colorectal cancer biomarkers. Tumour Biol 2019; 41:1010428319883721. [PMID: 31718480 DOI: 10.1177/1010428319883721] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The involvement of microRNA in cancers plays a significant role in their pathogenesis. Specific expressions of these non-coding RNAs also serve as biomarkers for early colorectal cancer diagnosis, but their laboratory/molecular identification is challenging and expensive. The aim of this study was to identify potential microRNAs for colorectal cancer diagnosis using in silico approach. Sequence similarity search was employed to obtain the candidate microRNA from the datasets, and three target prediction software were employed to determine their target genes. To determine the involvement of these microRNAs in colorectal cancer, the microRNA gene list obtained was used alongside with colorectal cancer expressed genes from gbCRC and CoReCG databases for gene intersection analysis. The involvement of these genes in the cancer subtype was further strengthened with the DAVID database. KEGG and Gene Ontology were used for the pathway and functional analysis, while STRING was employed for the interactions of protein network and further visualized by Cytoscape. The cBioPortal database was used to prioritize the target genes; prognostic and expression analysis were finally performed on the candidate microRNAs and the prioritized targets. This study, therefore, identified five candidate microRNAs, two hub genes (CTNNB1 and epidermal growth factor receptor), and seven significant target genes associated with colorectal cancer. The molecular validation studies are ongoing to ascertain the biological fitness of these findings.
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Affiliation(s)
- Adewale Oluwaseun Fadaka
- Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Bellville, South Africa
| | - Ashwil Klein
- Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Bellville, South Africa
| | - Ashley Pretorius
- Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Bellville, South Africa
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Asadi M, Talesh ST, Gjerstorff MF, Shanehbandi D, Baradaran B, Hashemzadeh S, Zafari V. Identification of miRNAs correlating with stage and progression of colorectal cancer. COLORECTAL CANCER 2019. [DOI: 10.2217/crc-2018-0014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Aim: miRNAs control biological processes that are implicated in carcinogenesis, and have been researched as potential biomarkers for colorectal cancer (CRC). The aim of the current study was to evaluate the miRNA expression profile in CRC patients to determine their potential to be used as biomarkers in the disease. Materials & methods: Total 47 tissues and their matched marginal tissues, as control group, were obtained from CRC patients. The transcript levels of a selected panel of 15 cancer-associated miRNAs were quantified via real-time gene expression method. Results: miR-155, miR130a, miR-181b, miR-196a, miR-200c and miR-224 were significantly upregulated, while miR122, miR-132, miR-203b, miR330, miR-323, miR-378a-3p and miR-598 we significantly downregulated in CRC. Conclusion: We identified a panel of miRNAs that may be involved in the etiology and pathogenesis of CRC, and may be used for novel diagnostic and therapeutic strategies.
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Affiliation(s)
- Milad Asadi
- Liver & Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shoan Taheri Talesh
- Hematology & Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morten Frier Gjerstorff
- Department of Cancer & Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Dariush Shanehbandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahriar Hashemzadeh
- Hematology & Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of General and Thoracic Surgery, Tabriz University of Medical Sciences, Imam Reza Hospital, Tabriz, Iran
| | - Venus Zafari
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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50
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Wang Y, Mu L, Huang M. MicroRNA‑195 suppresses rectal cancer growth and metastasis via regulation of the PI3K/AKT signaling pathway. Mol Med Rep 2019; 20:4449-4458. [PMID: 31702045 PMCID: PMC6797947 DOI: 10.3892/mmr.2019.10717] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 07/15/2019] [Indexed: 12/18/2022] Open
Abstract
MicroRNAs (miRNAs) play a vital role in the progression of cancer, however, only limited data on miRNAs in rectal cancer are available. The aim of the present study was to investigate whether miR‑195 could inhibit the progression of rectal cancer. The miR‑195 mimic was transfected into 2 types of human rectal cancer cells (SW837 and SW1463). Cell viability and apoptosis were analyzed by Cell Counting Kit‑8 (CCK‑8) assay and flow cytometry, and cell migration and invasion were assessed by scratch test and Transwell assay. The results revealed that insulin‑like growth factor 1 (IGF1) was predicted as a potential target of miR‑195 by Targetscan7.2, and the result was verified by dual‑luciferase reporter assay. The co‑transfection of IGF1 was performed to confirm the underlying mechanism of tumor suppressor of miR‑195 in rectal cancer. The activation of PI3K/AKT signaling was determined by western blotting. The levels of miR‑195 in SW837 and SW1463 cells were revealed to be lower than in human rectal mucosa epithelial cells. After the transfection with miR‑195, the cell viability was decreased, while the apoptosis was significantly increased (SW837: 5.21% vs. 20.96%; SW1463: 4.19% vs. 25.22%). Moreover, cell migration and invasion were significantly inhibited in the mimic group. miR‑195 specifically targeted IGF1, however, the co‑transfection of IGF1 could partially reverse the inhibitory effects of miR‑195 on rectal cancer cells. It was also determined that the phosphorylation of PI3K and AKT were significantly inhibited in the mimic group. The tumor suppressive ability of miR‑195 in rectal cancer cell proliferation and metastasis was mediated by blocking IGF1 expression and inhibiting the PI3K/AKT pathway.
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Affiliation(s)
- Yeli Wang
- Department of Anorectal, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Linsong Mu
- Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Miaoling Huang
- Department of Anorectal, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
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