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Lebedeva EI, Shchastniy AT, Babenka AS, Zinovkin DA, Nadyrov EA. Relationship between Genes and microRNAs Involved in the Migration of Cells from the Bone Marrow during Experimental Liver Fibrosis. Bull Exp Biol Med 2025; 178:351-359. [PMID: 39945950 DOI: 10.1007/s10517-025-06335-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Indexed: 02/28/2025]
Abstract
Progressive toxic liver fibrosis in Wistar male rats was characterized by the migration of CX3CR1+ and CD34+ cells from the bone marrow, accompanied by a mild increase in their numbers. From weeks 3 to 5 and 9 to 13, the number of CX3CR1+ cells remained approximately the same. The area occupied by CD34+ cells increased by 2 times (p<0.001) only by the end of the experiment. At week 3, the correlation between Cxcl12 and Notch2 mRNA was lost, while at week 9, a correlation of Cxcl12 with Notch1 and Notch2 was observed. From week 11 onwards, a correlation of Cxcl12 with Notch2 was revealed and a correlation with Notch1 disappeared. miR-3558-3p was correlated with Cxcl12 mRNA level at the stages of progressive fibrosis and nodular remodeling of the liver parenchyma. The greatest number of miRNAs showed direct and inverse correlations of moderate to medium strength, with Cxcl12 gene at the stage of complete cirrhosis. The mRNA levels of Cxcl12 and Yap1 showed a significant correlation with each other throughout the experiment. This suggests that they may be involved in the process of cell migration from the bone marrow to the liver and play a role in fibrosis and cirrhosis. They could be considered as potential targets for the development of new treatments.
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MESH Headings
- Animals
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Male
- Rats
- Chemokine CXCL12/genetics
- Chemokine CXCL12/metabolism
- Rats, Wistar
- Cell Movement/genetics
- Liver/pathology
- Liver/metabolism
- YAP-Signaling Proteins/metabolism
- YAP-Signaling Proteins/genetics
- Bone Marrow Cells/metabolism
- Bone Marrow Cells/pathology
- CX3C Chemokine Receptor 1/genetics
- CX3C Chemokine Receptor 1/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Receptor, Notch2/genetics
- Receptor, Notch2/metabolism
- Antigens, CD34/metabolism
- Antigens, CD34/genetics
- Receptor, Notch1/genetics
- Receptor, Notch1/metabolism
- Liver Cirrhosis/genetics
- Liver Cirrhosis/pathology
- Liver Cirrhosis/metabolism
- Liver Cirrhosis, Experimental/genetics
- Liver Cirrhosis, Experimental/pathology
- Liver Cirrhosis, Experimental/chemically induced
- Liver Cirrhosis, Experimental/metabolism
- Bone Marrow/pathology
- Bone Marrow/metabolism
- Carbon Tetrachloride/toxicity
- Gene Expression Regulation
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Affiliation(s)
- E I Lebedeva
- Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, Republic of Belarus.
| | - A T Shchastniy
- Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, Republic of Belarus
| | - A S Babenka
- Belarusian State Medical University, Minsk, Republic of Belarus
| | - D A Zinovkin
- Gomel State Medical University, Gomel, Republic of Belarus
| | - E A Nadyrov
- Gomel State Medical University, Gomel, Republic of Belarus
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2
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Zhu Y, He Y, Gan R. Wnt Signaling in Hepatocellular Carcinoma: Biological Mechanisms and Therapeutic Opportunities. Cells 2024; 13:1990. [PMID: 39682738 PMCID: PMC11640042 DOI: 10.3390/cells13231990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/19/2024] [Accepted: 12/01/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatocellular carcinoma (HCC), characterized by significant morbidity and mortality rates, poses a substantial threat to human health. The expression of ligands and receptors within the classical and non-classical Wnt signaling pathways plays an important role in HCC. The Wnt signaling pathway is essential for regulating multiple biological processes in HCC, including proliferation, invasion, migration, tumor microenvironment modulation, epithelial-mesenchymal transition (EMT), stem cell characteristics, and autophagy. Molecular agents that specifically target the Wnt signaling pathway have demonstrated significant potential for the treatment of HCC. However, the precise mechanism by which the Wnt signaling pathway interacts with HCC remains unclear. In this paper, we review the alteration of the Wnt signaling pathway in HCC, the mechanism of Wnt pathway action in HCC, and molecular agents targeting the Wnt pathway. This paper provides a theoretical foundation for identifying molecular agents targeting the Wnt pathway in hepatocellular carcinoma.
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Affiliation(s)
| | | | - Runliang Gan
- Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China; (Y.Z.); (Y.H.)
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Zhang Y, Da Yang G, Chen QY, Zeng J, Cao Y. Microrna-342 inhibits hepatocellular carcinoma cell proliferation and promotes apoptosis through the FOXP1/MYCBP Signaling Axis. Toxicol Res (Camb) 2024; 13:tfae149. [PMID: 39698396 PMCID: PMC11649998 DOI: 10.1093/toxres/tfae149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/13/2024] [Accepted: 08/20/2024] [Indexed: 12/20/2024] Open
Abstract
To investigate the role and mechanism of miR-342 and FOXP1 on hepatocellular carcinoma cells. QRT-PCR was applied to determine the expression of miR-342, FOXP1 and MYCBP in normal hepatocyte cell lines (NHC), hepatocellular carcinoma cell lines (HEK-293 T) and human hepatocellular carcinoma cell lines (HepG2, MHCC97-L, Huh7 and SMMC7721). After knockdown or over-expression of miR-342 and FOXP1 in HepG2 cells respectively, cell proliferation and cell viability were measured using MTT assay and colony formation assay. Flow cytometry was adopted to test for apoptosis. Dual luciferase gene reporter assays were performed to validate the target relationship between FOXP1and miR-342 or MYCBP. The level of apoptosis-related proteins cleaved-caspase-3, Bcl-2 and Bax were measured by western blot. Compared with NHC, miR-342 expression was decreased and FOXP1 expression was up-regulated in hepatocellular carcinoma cell lines. MiR-342 could target and negatively regulate FOXP1. FOXP1 could promote the proliferation of hepatocellular carcinoma cells, positively regulate the expression of c-Caspase-3, Bax, negatively regulate Bcl-2 and inhibit apoptosis. FOXP1 can also target and positively regulate MYCBP. The expression of MYCBP was up-regulated in the hepatocellular carcinoma cell lines, while overexpression of miR-342 decreased MYCBP expression promoted by overexpression of FOXP1. MiR-342 can inhibit FOXP1/MYCBP signaling axis to regulate the members of Caspase-3 and Bcl-2 family to inhibit the proliferation and promote apoptosis of hepatocellular carcinoma cells.
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Affiliation(s)
- Yanling Zhang
- Department of Oncology, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 232, Outer Ring East Road, Panyu District, Guangzhou 510000 Guangdong Province, China
- The First Clinical School of Guangzhou University of Chinese Medicine, No. 1 Guangming East Road, Zengcheng District, Guangzhou 510000 Guangdong Province, China
| | - Guang Da Yang
- Department of Oncology, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 232, Outer Ring East Road, Panyu District, Guangzhou 510000 Guangdong Province, China
- The First Clinical School of Guangzhou University of Chinese Medicine, No. 1 Guangming East Road, Zengcheng District, Guangzhou 510000 Guangdong Province, China
| | - Qian Ya Chen
- Department of Oncology, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 232, Outer Ring East Road, Panyu District, Guangzhou 510000 Guangdong Province, China
- The First Clinical School of Guangzhou University of Chinese Medicine, No. 1 Guangming East Road, Zengcheng District, Guangzhou 510000 Guangdong Province, China
| | - Jinlong Zeng
- Department of Oncology, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 232, Outer Ring East Road, Panyu District, Guangzhou 510000 Guangdong Province, China
- The First Clinical School of Guangzhou University of Chinese Medicine, No. 1 Guangming East Road, Zengcheng District, Guangzhou 510000 Guangdong Province, China
| | - Yang Cao
- Department of Oncology, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 232, Outer Ring East Road, Panyu District, Guangzhou 510000 Guangdong Province, China
- The First Clinical School of Guangzhou University of Chinese Medicine, No. 1 Guangming East Road, Zengcheng District, Guangzhou 510000 Guangdong Province, China
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Samy AM, Kandeil MA, Sabry D, Abdel-Ghany AA, Mahmoud MO. Exosomal miR-122, miR-128, miR-200, miR-298, and miR-342 as novel diagnostic biomarkers in NAFL/NASH: Impact of LPS/TLR-4/FoxO3 pathway. Arch Pharm (Weinheim) 2024; 357:e2300631. [PMID: 38574101 DOI: 10.1002/ardp.202300631] [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: 10/30/2023] [Accepted: 12/19/2023] [Indexed: 04/06/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder affecting a quarter of the global residents. Progression of NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, liver cancer, and failure. Gut microbiota imbalance causes microbial components translocation into the circulation, triggering liver inflammation and NASH-related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic and prognostic biomarkers for NAFL and NASH liver damage. Our work investigated the role of the gut microbiota in NAFLD pathogenesis via the lipopolysaccharide/toll-like receptor 4/Forkhead box protein O3 (LPS/TLR-4/FoxO3) pathway and certain miRNAs as noninvasive biomarkers for NAFL or its development to NASH. miRNA expression levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 NAFL patients, 50 NASH patients, and 50 normal controls. Plasma LPS, TLR-4, adiponectin, peroxisome proliferator-activated receptor γ (PPAR-γ), and FoxO3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In NAFL and NASH patients, miR-122, miR-128, FoxO3, TLR-4, LPS, and PPAR-γ were upregulated while miR-200, miR-298, miR-342, and adiponectin were downregulated compared with the normal control. The examined miRNAs might distinguish NAFL and NASH patients from the normal control using receiver operating characteristic analysis. Our study is the first to examine these miRNAs in NAFLD. Our findings imply that these are potentially promising biomarkers for noninvasive early NAFL diagnosis and NASH progression. Understanding the LPS/TLR-4/FoxO3 pathway involvement in NAFL/NASH pathogenesis may aid disease management.
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Affiliation(s)
- Ahmed M Samy
- Department of Biochemistry, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
| | - Mohamed A Kandeil
- Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Dina Sabry
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University in Cairo, Cairo, Egypt
| | - A A Abdel-Ghany
- Department of Biochemistry, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assuit branch, Egypt
| | - Mohamed O Mahmoud
- Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
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5
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Chen Y, Tan X, Zhang W, Li Y, Deng X, Zeng J, Huang L, Ma X. Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives. Phytother Res 2024; 38:1623-1650. [PMID: 38302697 DOI: 10.1002/ptr.8103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 12/07/2023] [Accepted: 12/16/2023] [Indexed: 02/03/2024]
Abstract
Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.
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Affiliation(s)
- Yuan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiyue Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wenwen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yubing Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinyu Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lihua Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Gajos-Michniewicz A, Czyz M. WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities. Genes Dis 2024; 11:727-746. [PMID: 37692481 PMCID: PMC10491942 DOI: 10.1016/j.gendis.2023.02.050] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 12/28/2022] [Accepted: 02/14/2023] [Indexed: 09/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a liver cancer, highly heterogeneous both at the histopathological and molecular levels. It arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways, including canonical WNT/β-catenin, AKT/mTOR, MAPK pathways as well as signaling associated with telomere maintenance, p53/cell cycle regulation, epigenetic modifiers, and oxidative stress. The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established, whereas in development and progression of HCC is extensively studied. Herein, we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development, acquisition of stemness features, metastasis, and resistance to treatment. We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC. We discuss the pivotal roles of CTNNB1 mutations, aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.
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Affiliation(s)
- Anna Gajos-Michniewicz
- Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz 92-215, Poland
| | - Malgorzata Czyz
- Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz 92-215, Poland
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Hajizadeh M, Hajizadeh F, Ghaffarei S, Amin Doustvandi M, Hajizadeh K, Yaghoubi SM, Mohammadnejad F, Khiabani NA, Mousavi P, Baradaran B. MicroRNAs and their vital role in apoptosis in hepatocellular carcinoma: miRNA-based diagnostic and treatment methods. Gene 2023; 888:147803. [PMID: 37716587 DOI: 10.1016/j.gene.2023.147803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 08/03/2023] [Accepted: 09/13/2023] [Indexed: 09/18/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies with high invasive and metastatic capability. Although significant advances have been made in the treatment of HCC, the overall survival rate of patients is still low. It is essential to explore accurate biomarkers for early diagnosis and prognosis along with therapeutic procedures to increase the survival rate of these patients. Anticancer therapies can contribute to induce apoptosis for the elimination of cancerous cells. However, dysregulated apoptosis and proliferation signaling pathways lead to treatment resistance, a significant challenge in improving efficient therapies. MiRNAs, short non-coding RNAs, play crucial roles in the progression of HCC, which regulate gene expression through post-transcriptional inhibition and targeting mRNA degradation in cancers. Dysregulated expression of multiple miRNAs is associated with numerous biological processes, including cell proliferation, apoptosis, invasion and metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug resistance in HCC. This review summarizes the role and potential efficacy of miRNAs in promoting and inhibiting cell proliferation and apoptosis in HCC, as well as the role of miRNAs in therapy resistance in HCC.
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Affiliation(s)
- Masoumeh Hajizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farnaz Hajizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sevil Ghaffarei
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Khadijeh Hajizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyed Mohammad Yaghoubi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | | | | | - Pegah Mousavi
- 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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Alidoost Z, Attari F, Saadatpour F, Arefian E. Inhibitory effect of miR342 on the progression of triple-negative breast cancer cells in vitro and in the mice model. BIOIMPACTS : BI 2023; 14:27758. [PMID: 38327636 PMCID: PMC10844590 DOI: 10.34172/bi.2023.27758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 04/05/2023] [Accepted: 06/12/2023] [Indexed: 02/09/2024]
Abstract
Introduction Breast cancer is the most common cancer in women worldwide, and the triple-negative subtype is the most invasive, with limited therapeutic options. Since miRNAs are involved in many cellular processes, they harbor great value for cancer treatment. Therefore, in this study, we have investigated the anti-proliferative and anti-invasive roles of miR342 in 4T1 triple-negative cells in vitro and also studied the effect of this miRNA on tumor progression and the expression of its target genes in vivo. Methods 4T1 cells were transduced with conditioned media of miR342-transfected Hek-LentiX cells. MTT and clonogenic assays were used to assess the viability and colony-forming ability of 4T1 cells. Apoptosis and invasion rates were respectively evaluated by annexin/7-AAD and wound healing assays. At last, in vivo tumor progression was evaluated using H&E staining, real-time PCR, and immunohistochemistry. Results The viability of transduced-4T1 cells reduced significantly 48 hours after cell seeding and colony forming ability of these cells reduced to 50% of the control group. Also, miR342 imposed apoptotic and anti-invasive influence on these cells in vitro. A 30-day follow-up of the breast tumor in the mice model certified significant growth suppression along with reduced mitotic index and tumor grade in the treatment group. Moreover, decreased expression of Bcl2l1, Mcl1, and ID4, as miR342 target genes, was observed, accompanied by reduced expression of VEGF and Bcl2/Bax ratio at the protein level. Conclusion To conclude, our data support the idea that miR342 might be a potential therapeutic target for the treatment of triple-negative breast cancer (TNBC).
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Affiliation(s)
- Zahra Alidoost
- Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Farnoosh Attari
- Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Fatemeh Saadatpour
- Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Ehsan Arefian
- Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
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Ruiz-Manriquez LM, Carrasco-Morales O, Sanchez Z EA, Osorio-Perez SM, Estrada-Meza C, Pathak S, Banerjee A, Bandyopadhyay A, Duttaroy AK, Paul S. MicroRNA-mediated regulation of key signaling pathways in hepatocellular carcinoma: A mechanistic insight. Front Genet 2022; 13:910733. [PMID: 36118880 PMCID: PMC9478853 DOI: 10.3389/fgene.2022.910733] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 08/10/2022] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. The molecular pathogenesis of HCC varies due to the different etiologies and genotoxic insults. The development of HCC is characterized by complex interactions between several etiological factors that result in genetic and epigenetic changes in proto-onco and/or tumor suppressor genes. MicroRNAs (miRNAs) are short non-coding RNAs that also can act as oncomiRs or tumor suppressors regulating the expression of cancer-associated genes post-transcriptionally. Studies revealed that several microRNAs are directly or indirectly involved in cellular signaling, and dysregulation of those miRNAs in the body fluids or tissues potentially affects key signaling pathways resulting in carcinogenesis. Therefore, in this mini-review, we discussed recent progress in microRNA-mediated regulation of crucial signaling networks during HCC development, concentrating on the most relevant ones such as PI3K/Akt/mTOR, Hippo-YAP/TAZ, and Wnt/β-catenin, which might open new avenues in HCC management.
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Affiliation(s)
| | | | - E. Adrian Sanchez Z
- Tecnologico de Monterrey, School of Engineering and Sciences, Queretaro, Mexico
| | | | | | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, India
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, India
| | - Anindya Bandyopadhyay
- International Rice Research Institute, Manila, Philippines
- Reliance Industries Ltd., Navi Mumbai, India
| | - Asim K. Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Queretaro, Mexico
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Interplays between non-coding RNAs and chemokines in digestive system cancers. Biomed Pharmacother 2022; 152:113237. [PMID: 35716438 DOI: 10.1016/j.biopha.2022.113237] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 11/24/2022] Open
Abstract
Within tumors, chemokines and their cognate receptors are expressed by infiltrated leukocytes, cancerous cells, and related cells of stroma, like tumor-associated fibroblasts and tumor-associated macrophages. In malignancies, the altered expression of chemokines/chemokine receptors governs leukocyte infiltration and activation, epithelial-mesenchymal transition (EMT), cancer cell proliferation, angiogenesis, and metastasis. Non-coding RNAs (ncRNAs) contribute to multiple physiological and pathophysiological processes. Some miRNAs can exert anti-tumorigenic activity in digestive system malignancies by repressing the expression of tumor-promoting chemokines/chemokine receptors or by upregulating tumor-suppressing chemokines/chemokine receptors. However, many miRNAs exert pro-tumorigenic activity by suppressing the expression of chemokines/chemokine receptors or by upregulating tumor-promoting chemokines/chemokine receptors. LncRNA and circRNAs also exert pro- and anti-tumorigenic effects by targeting downstream miRNAs influencing the expression of tumor-promoting and tumor-suppressor chemokines/chemokine receptors. On the other side, some chemokines influence the expression of ncRNAs affecting tumor formation. The current review explains the communications between ncRNAs and chemokines/chemokine receptors in certain digestive system malignancies, such as gastric, colorectal, and pancreatic cancers and hepatocellular carcinoma to gain better insights into their basic crosstalk as well as possible therapeutic modalities.
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11
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Zhou Q, Liu ZZ, Wu H, Kuang WL. LncRNA H19 Promotes Cell Proliferation, Migration, and Angiogenesis of Glioma by Regulating Wnt5a/β-Catenin Pathway via Targeting miR-342. Cell Mol Neurobiol 2022; 42:1065-1077. [PMID: 33161527 PMCID: PMC11441209 DOI: 10.1007/s10571-020-00995-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 11/01/2020] [Indexed: 11/30/2022]
Abstract
Glioma is the most common malignant brain tumor and long non-coding RNAs (lncRNAs) have been reported to play an important role in the growth and angiogenesis of glioma. However, the potential mechanisms of lncRNA H19 in glioma remain unclear. In the present study, the effects of lncRNA H19 on glioma cell proliferation, migration, and angiogenesis were evaluated. The expression levels of H19, miR-342, and Wnt5a in glioma tissues and cells were detected by RT-qPCR or Western blotting. Dual luciferase reporter assay confirmed the interaction between H19, miR-342, and Wnt5a. Cell proliferation, migration, and angiogenesis were analyzed by colony formation, transwell, and tube formation assays, respectively. IHC was performed to test the angiogenesis-related factor CD31. H19 and Wnt5a expression were remarkably upregulated in glioma tissues and cells, whereas miR-342 expression was downregulated. Moreover, functional analysis confirmed that knockdown of H19 or overexpression of miR-342 suppressed glioma cell proliferation, migration, and angiogenesis in vitro. Besides, H19 was found to directly target miR-342 to promote Wnt5a expression and activate β-catenin pathway in glioma cells. Moreover, suppression of miR-342 or overexpression of Wnt5a reversed the inhibitory effect of sh-H19 on glioma growth and metastasis. Additionally, we verified that H19 promoted glioma cell proliferation, migration, and angiogenesis via miR-342/Wnt5a/β-catenin axis in vivo. H19 regulates glioma cell growth and metastasis through miR-342 to mediate Wnt5a/β-catenin signaling pathway, which provides new therapeutic targets for glioma treatment.
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Affiliation(s)
- Qin Zhou
- Department of Oncology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan Province, People's Republic of China
| | - Zheng-Zheng Liu
- Department of Oncology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan Province, People's Republic of China
| | - Heng Wu
- Department of Internal Medicine, Qidong Hospital of Traditional Chinese Medicine, Hengyang, 421600, Hunan Province, People's Republic of China
| | - Wei-Lu Kuang
- Department of Oncology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan Province, People's Republic of China.
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Cui Z, Song Q, Chen Y, Yang K. Construction of miRNA-mRNA regulatory network and analysis of hub genes in oral squamous cell carcinoma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2022; 166:280-289. [PMID: 35132271 DOI: 10.5507/bp.2022.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 01/19/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. METHODS The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. RESULTS A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. CONCLUSIONS The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.
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Affiliation(s)
- Zifeng Cui
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang 050000, Hebei, China
| | - Qiwen Song
- Oral and Maxillofacial Surgery, Hebei Provincial Stomatological Hospital, No. 383, East Zhongshan Road, Shijiazhuang 050000, Hebei, China
| | - Yanping Chen
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang 050000, Hebei, China
| | - Kaicheng Yang
- Department of Stomatology, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang 050000, Hebei, China
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Wei XC, Xia YR, Zhou P, Xue X, Ding S, Liu LJ, Zhu F. Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma. World J Gastroenterol 2021; 27:8302-8322. [PMID: 35068871 PMCID: PMC8717014 DOI: 10.3748/wjg.v27.i48.8302] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/22/2021] [Accepted: 11/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The association of hepatitis B virus (HBV) infection with HCC is hitherto documented. Exosomal miRNAs contribute to cancer progression and chemoresistance. HBV X protein has been known to modulate miRNAs that facilitate cell proliferation and the process of hepatocarcinogenesis. However, there has been no report on hepatitis B core antigen (HBc) regulating exosomal miRNAs to induce drug resistance of HCC cells. AIM To elucidate the mechanism by which HBc promotes Doxorubicin hydrochloride (Dox) resistance in HCC. METHODS Exosomes were isolated by ultracentrifugation. The morphology and size of exosomes were evaluated by Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM). The miRNAs differentially expressed in HCC were identified using The Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissue samples was detected by quantitative polymerase chain reaction. TargetScan and luciferase assay were used to predict and prove the target gene of miR-135a-5p. Finally, we identified the effects of miR-135a-5p on anti-apoptosis and the proliferation of HCC in the presence or absence of Dox using flow cytometry, Cell counting kit 8 (CCK-8) assay and western blot. RESULTS We found that HBc increased the expression of exosomal miR-135a-5p. Integrated analysis of bioinformatics and patient samples found that miR-135a-5p was increased in HCC tissues in comparison with paracancerous tissues. Bioinformatic analysis and in vitro validation identified vesicle-associated membrane protein 2 (VAMP2) as a novel target gene of miR-135a-5p. Functional assays showed that exosomal miR-135a-5p induced apoptosis protection, cell proliferation, and chemotherapy resistance in HCC. In addition, the rescue experiment demonstrated that VAMP2 reversed apoptosis protection, cell growth, and drug resistance by miR-135a-5p. Finally, HBc promoted HCC anti-apoptosis, proliferation, and drug resistance and prevented Dox-induced apoptosis via the miR-135a-5p/VAMP2 axis. CONCLUSION These data suggested that HBc upregulated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2. Thus, our work indicated an essential role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC and a potential molecular therapeutic target for HCC.
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Affiliation(s)
- Xiao-Cui Wei
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Ya-Ru Xia
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Ping Zhou
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Xing Xue
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Shuang Ding
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Li-Juan Liu
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Fan Zhu
- State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
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Deldar Abad Paskeh M, Mirzaei S, Ashrafizadeh M, Zarrabi A, Sethi G. Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways. J Hepatocell Carcinoma 2021; 8:1415-1444. [PMID: 34858888 PMCID: PMC8630469 DOI: 10.2147/jhc.s336858] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/05/2021] [Indexed: 12/14/2022] Open
Abstract
Liver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains a challenging disease to treat. Wnt/β-catenin signaling pathway is considered a tumor-promoting factor in various cancers; hence, the present review focused on the role of Wnt signaling in HCC, and its association with progression and therapy response based on pre-clinical and clinical evidence. The nuclear translocation of β-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding β-catenin and its overexpression can lead to HCC progression. β-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, β-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that β-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate β-catenin signaling in HCC. Anti-cancer agents inhibit β-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of β-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/β-catenin signaling in HCC therapy.
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Affiliation(s)
- Mahshid Deldar Abad Paskeh
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul, Turkey
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul, Turkey
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul, Turkey
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul, 34396, Turkey
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Cancer Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Chang Y, Deng Q, Guan Z, Cheng Y, Sun Y. MiR-1273 g-3p Promotes Malignant Progression and has Prognostic Implications in Prostate Cancer. Mol Biotechnol 2021; 64:17-24. [PMID: 34431044 DOI: 10.1007/s12033-021-00384-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 08/16/2021] [Indexed: 12/22/2022]
Abstract
Prostate cancer (PCa) is the most popular cancer of mankind. Our study aimed to provide the expression and the predictive significance of miR-1273 g-3p in PCa. Moreover, the effects on cell biological activities were also investigated. The relative expression of miR-1273 g-3p in PCa tissues and cell lines was validated by quantitative real-time PCR. Kaplan-Meier curve and Cox regression analyses were performed to indicate the prognostic value. The implications of miR-1273 g-3p on cell proliferation, migration, and invasion were validated using the CCK-8 and Transwell assay. Our results provided that the expression of miR-1273 g-3p was increased in PCa tissues and cell lines. The levels of miR-1273 g-3p were associated with Gleason score, TNM stage, clinical stage, and lymph node metastasis. Overexpression of miR-1273 g-3p indicated a promising overall survival rate. Cox regression results indicated miR-1273 g-3p might be an independent marker for PCa patients. Silenced miR-1273 g-3p inhibited PCa cell proliferation, migration, and invasion. In total, miR-1273 g-3p was increased in PCa and identified as a therapeutic target and a prognostic factor for PCa patients. Overexpression of miR-1273 g-3p might be an oncogene via accelerating cell proliferation, migration, and invasion.
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Affiliation(s)
- Yaxue Chang
- Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
| | - Qian Deng
- Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
| | - Zhenfeng Guan
- Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
| | - Yongyi Cheng
- Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
| | - Yi Sun
- Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
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Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis. J Neurooncol 2021; 154:131-144. [PMID: 34357490 DOI: 10.1007/s11060-021-03814-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/23/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma. METHODS The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3. RESULTS The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3. CONCLUSION Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.
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Wang J, Zhang C, Chen X, Li Y, Li A, Liu D, Li F, Luo T. Functions of CXC chemokines as biomarkers and potential therapeutic targets in the hepatocellular carcinoma microenvironment. Transl Cancer Res 2021; 10:2169-2187. [PMID: 35116536 PMCID: PMC8797652 DOI: 10.21037/tcr-21-127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/26/2021] [Indexed: 12/16/2022]
Abstract
Background Several studies have indicated that CXC chemokines influence the prognosis and therapy in patients with hepatocellular carcinoma (HCC). However, there are limited studies on the roles of CXC chemokines in HCC based on data acquired from various databases. This study aimed to conduct an in-depth and comprehensive bioinformatic analysis of the expression and functions of CXC chemokines in HCC. Methods Data was obtained from various databases including ONCOMINE, UALCAN, STRING, GeneMinia, DAVID, Kaplan-Meier plotter, TIMER, GSCALite and NetworkAnalyst for the analysis of the expression and functions of the CXC chemokines in HCC. Results Analysis of the differential expression levels of CXC chemokines between HCC and adjacent normal tissues revealed that the mRNA expression levels of CXCL1/2/5/6/7/12/14 were significantly lower in HCC tissues than those in adjacent normal tissues, whereas the mRNA expression levels of CXCL9/16/17 were significantly higher in HCC tissues. Analysis of the relationship between CXC chemokines and overall survival revealed that high mRNA expression levels of CXCL1/3/5/6/8 were associated with poor overall survival, whereas high mRNA expression levels of CXCL2/4/7/9/10/12 were associated with better overall survival. The functions of CXC chemokines and related genes were associated with cytokine-cytokine receptor interactions and chemokine signaling pathway. Analysis of the association between CXC chemokines and activity of cancer pathways indicated that the DNA damage response and hormone androgen receptor (AR) signaling pathways were inhibited, whereas apoptosis, epithelial-mesenchymal transition (EMT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways were activated. The expression of CXC chemokines was positively correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells). Conclusions This study has demonstrated that CXC chemokines can influence survival of patients with HCC by recruiting different types of immune cells into the tumor microenvironment.
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Affiliation(s)
- Jukun Wang
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chao Zhang
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xin Chen
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yu Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Ang Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Dongbin Liu
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tao Luo
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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Komoll RM, Hu Q, Olarewaju O, von Döhlen L, Yuan Q, Xie Y, Tsay HC, Daon J, Qin R, Manns MP, Sharma AD, Goga A, Ott M, Balakrishnan A. MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma. J Hepatol 2021; 74:122-134. [PMID: 32738449 DOI: 10.1016/j.jhep.2020.07.039] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a cancer with multiple aetiologies and widespread prevalence. Largely refractory to current treatments, HCC is the fourth leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are important regulators in HCCs. We aimed to identify tumour suppressor miRNAs during tumour regression in a conditional c-MYC-driven mouse model (LT2/MYC) of HCC, and to evaluate their therapeutic potential for HCC treatment. METHODS We performed miRNA expression profiling of developed and regressing LT2/MYC tumours and in-depth in vitro gain- and loss-of-function analyses. The effect of adeno-associated virus (AAV) vector-mediated miR-342-3p treatment was evaluated in 3 HCC mouse models. RESULTS We identified miR-342-3p as a tumour suppressor miRNA in HCC, with increased expression in regressing tumours. Forced miR-342-3p expression in hepatoma cells showed significantly decreased cell proliferation, migration, and colony formation. In vivo administration of AAV-miR-342-3p led to significant attenuation of tumour development and increased overall survival. We identified monocarboxylic acid transporter 1 (MCT1) as a bona fide target of miR-342-3p in HCC. We show that the tumour suppressor role of miR-342-3p is executed partly by modulating the lactate transport function of MCT1. Importantly, we find miR-342-3p downregulated in tumours from patients with HCC compared with matched non-tumour tissues, inversely correlating with MCT1 expression. We observed similar findings in TCGA-LIHC data. CONCLUSIONS In our study, we identified and validated miR-342-3p as a tumour suppressor miRNA in HCC. We demonstrated its therapeutic efficacy in significantly attenuating tumour development, and prolonging survival, in different HCC mouse models. Identification of miR-342-3p as an effective tumour suppressor opens a therapeutic avenue for miRNA-mediated attenuation of HCC development. LAY SUMMARY Hepatocellular carcinoma (HCC), the most common type of liver cancer, affects diverse populations and has a global impact, being the fourth leading cause of cancer deaths worldwide. There are currently no systemic therapies for HCC that can significantly prolong long-term survival. Thus, novel effective treatment options are urgently required. To understand the molecular basis of tumour regression, we compared tumours and regressing liver tumours in mice. We show that a small non-coding miRNA, miR-342-3p, is a tumour suppressor in HCC. Expression of miR-342-3p is low in tumours and high in regressing tumours. When miR-342-3p is delivered to mouse livers with HCC, it can significantly slow down liver tumour development and improve survival. Our study highlights the promising therapeutic potential of miR-342-3p intervention in HCC.
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Affiliation(s)
- Ronja-Melinda Komoll
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Qingluan Hu
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Olaniyi Olarewaju
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Lena von Döhlen
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Qinggong Yuan
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Yu Xie
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hsin-Chieh Tsay
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Joel Daon
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Amar Deep Sharma
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover, Germany
| | - Andrei Goga
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA
| | - Michael Ott
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany
| | - Asha Balakrishnan
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
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Xiong X, Xu W, Gong J, Wang L, Dai M, Chen G, Yuan L. miR-937-5p targets SOX17 to modulate breast cancer cell cycle and cell proliferation through the Wnt signaling pathway. Cell Signal 2020; 77:109818. [PMID: 33144185 DOI: 10.1016/j.cellsig.2020.109818] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 09/25/2020] [Accepted: 10/22/2020] [Indexed: 12/18/2022]
Abstract
Breast cancer is one of the most frequent cancers in women and the globally leading cause of cancer-related deaths. Bioinformatics and experimental analyses found that miR-937-5p may play a proto-oncogenic role in breast cancer; however, the specific effects and the molecular mechanism need further investigation. GSEA-KEGG and GSEA-GO suggested that miR-937-5p might be related to cell cycle and DNA replication. The experimental data indicated that miR-937-5p inhibition significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest. Meanwhile, the protein levels of proliferating marker ki-67 and cell cycle regulators Cyclin A2, Cyclin B1, CDK1, and Cyclin D1 were also decreased by miR-937-5p inhibition. miR-937-5p could directly bind to and negatively regulate SOX17. SOX17 overexpression also significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest and decreased ki-67, β-catenin, c-Myc, Cyclin A2, Cyclin B1, Cyclin D1, and CDK1 protein contents. More importantly, the effects of miR-937-5p were reversed by SOX17.
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Affiliation(s)
- Xiang Xiong
- Department of burn and plastic surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Wendi Xu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Jia Gong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Liwen Wang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Mei Dai
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Gannong Chen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Liqin Yuan
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
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Zhu S, Song W, Sun Y, Zhou Y, Kong F. MiR-342 attenuates lipopolysaccharide-induced acute lung injury via inhibiting MAPK1 expression. Clin Exp Pharmacol Physiol 2020; 47:1448-1454. [PMID: 32248545 DOI: 10.1111/1440-1681.13315] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/28/2020] [Accepted: 03/24/2020] [Indexed: 12/21/2022]
Abstract
Micro RNA (miRNA) and mitogen-activated protein kinase (MAPK) are reported as the crucial regulators of inflammatory responses in acute lung injury (ALI). This study will explore the role of the miR-342/MAPK1 axis in regulation of lipopolysaccharide (LPS)-induced ALI. We found that miR-342 was down-regulated in LPS-induced A549 cells compared with the control group with DMSO, accompanied by elevated inflammatory cytokines and apoptosis. Over-expression of miR-342 reduced LPS-induced inflammatory responses and apoptosis in LPS-stimulated A549 cells, and had a protective role in LPS-treated mice with ALI by decreasing levels of inflammatory cytokines, improving survival of mice with ALI, and ameliorating the lung permeability. Dual-luciferase reporter gene assay demonstrated that miR-342 regulated the expression of MAPK1 by directly targeting its 3' untranslated region (3'-UTR). Mechanistically, MAPK1 silencing abrogated LPS-induced inflammatory injury in A549 cells, and partially enhanced the protective effect of miR-342. Therefore, miR-342 attenuates LPS-induced ALI by targeting MAPK1 expression, thereby protecting against A549 cell injury induced by LPS and lung injury of mice with ALI.
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Affiliation(s)
- Siliang Zhu
- Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China
| | - Wenke Song
- Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China
| | - Yanqi Sun
- Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China
| | - Yongqin Zhou
- Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China
| | - Fanpo Kong
- Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China
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Chi X, Jiang Y, Chen Y, Lv L, Chen J, Yang F, Zhang X, Pan F, Cai Q. microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/β-catenin signaling pathway. Biomark Med 2020; 14:981-996. [PMID: 32940078 DOI: 10.2217/bmm-2019-0511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 05/22/2020] [Indexed: 12/12/2022] Open
Abstract
Aim: This study aimed to investigate the expression of microRNA-505 (miR-505) and explore its clinical significance, biological function and mechanisms in hepatocellular carcinoma (HCC). Methods: Expression of miR-505 was measured in 128 paired HCC tissues and five cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell migration, invasion assays and apoptosis assay were performed to explore the functional role of miR-505. The target gene of miR-505 was assessed using the bioinformatics assay and the related signaling pathway was confirmed using western blot. Results: Expression of miR-505 in HCC serum and tissues were downregulated. The overexpression of miR-505 in HCC cells inhibited cell proliferation and metastasis, as well as enhanced cell apoptosis by directly downregulating heterogeneous nuclear ribonucleoprotein M (HNRNPM). The activity of the Wnt/β-catenin signaling pathway was suppressed by the overexpression of miR-505 but was promoted by the upregulation of HNRNPM. Conclusion: The results suggest that the regulation of miR-505/HNRNPM may be a novel strategy to improve the targeted therapy of HCC.
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Affiliation(s)
- Xiaobin Chi
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Yi Jiang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Yongbiao Chen
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Lizhi Lv
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Jianwei Chen
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Fang Yang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Xiaojin Zhang
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Fan Pan
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
| | - Qiucheng Cai
- Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou 350025, China
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22
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Zalewski DP, Ruszel KP, Stępniewski A, Gałkowski D, Bogucki J, Komsta Ł, Kołodziej P, Chmiel P, Zubilewicz T, Feldo M, Kocki J, Bogucka-Kocka A. Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm. J Clin Med 2020; 9:jcm9061974. [PMID: 32599769 PMCID: PMC7355415 DOI: 10.3390/jcm9061974] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/13/2020] [Accepted: 06/22/2020] [Indexed: 12/16/2022] Open
Abstract
Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.
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Affiliation(s)
- Daniel P. Zalewski
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.C.)
| | - Karol P. Ruszel
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Andrzej Stępniewski
- Ecotech Complex Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Skłodowska, 39 Głęboka St., 20-612 Lublin, Poland;
| | - Dariusz Gałkowski
- Department of Pathology and Laboratory Medicine, Rutgers - Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USA;
| | - Jacek Bogucki
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Łukasz Komsta
- Chair and Department of Medicinal Chemistry, Medical University of Lublin, 4 Jaczewskiego St., 20-090 Lublin, Poland;
| | - Przemysław Kołodziej
- Laboratory of Diagnostic Parasitology, Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland;
| | - Paulina Chmiel
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.C.)
| | - Tomasz Zubilewicz
- Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland; (T.Z.); (M.F.)
| | - Marcin Feldo
- Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland; (T.Z.); (M.F.)
| | - Janusz Kocki
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Anna Bogucka-Kocka
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.C.)
- Correspondence: ; Tel.: +48-81-448-7232
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Du X, He W, He H, Wang H. Beta-catenin inhibits bovine parainfluenza virus type 3 replication via innate immunity pathway. BMC Vet Res 2020; 16:72. [PMID: 32127006 PMCID: PMC7055115 DOI: 10.1186/s12917-020-02291-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 02/18/2020] [Indexed: 02/07/2023] Open
Abstract
Background Bovine parainfluenza virus type 3 (BPIV3) is one of the important viral respiratory agents associated with the bovine respiratory disease complex (BRDC) in cattle. Previous study has demonstrated that infection of BPIV3 causes innate immune response within the host cell. β-catenin is a key component of the Wnt/β-catenin signal pathway which is involved in the regulation of interferon-beta (IFN-β) transcription. Some viruses can activate while others can inhibit the Wnt/β-catenin signaling pathway. However, the role of β-catenin in BPIV3 infection remains unclear. Results Here we found that the expression of β-catenin mRNA was up-regulated and β-catenin protein was down-regulated after BPIV3 infection in MDBK cells. Moreover, it was confirmed that overexpression of β-catenin suppressed BPIV3 replication and knockdown of β-catenin promoted viral replication, suggesting that β-catenin inhibits BPIV3 replication. Furthermore, IFN-β signal pathway and virus titer analysis using the GSK3β inhibitor (LiCl) revealed that Wnt/β-catenin can serve as a mechanism to suppress virus replication in infected cells. The results indicated that LiCl promoted the expression and accumulation in the nucleus of β-catenin, which further promoted the expression of IFN-β and OSA1 and suppressed BPIV3 replication. Most importantly, BPIV3 down-regulating β-catenin protein expression was due to degradation of GSK3β mediated proteasome pathway. Conclusions In summary, we discovered the relationship between β-catenin and BPIV3 replication. These results provided further insight into the study of BPIV3 pathogenesis.
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Affiliation(s)
- Xinying Du
- Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, 250014, China
| | - Wenqi He
- College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, China
| | - Hongbin He
- Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.
| | - Hongmei Wang
- Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.
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Liu H, Ma L, Wang L, Yang Y. MicroRNA-937 is overexpressed and predicts poor prognosis in patients with colon cancer. Diagn Pathol 2019; 14:136. [PMID: 31856857 PMCID: PMC6923914 DOI: 10.1186/s13000-019-0920-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 12/11/2019] [Indexed: 12/17/2022] Open
Abstract
Background Colon cancer is a heterogeneous tumor and a leading cause of cancer-related mortality. MicroRNA (miRNA) has been proposed as the biomarker in cancers. The aim of this study was to investigate the clinical significance and potential functional role of miR-937 in colon cancer. Methods In the present study, reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of miR-937 in colon cancer tissues and cell lines. Kaplan-Meier curve and Cox regression analyses were used to determine the prognostic impact of miR-937 on survival. Cell Counting Kit-8 and Transwell assays were performed to examine cell proliferation, migration, and invasion, respectively. Results miR-937 was significantly upregulated in colon cancer tissues and cell lines. Clinical analysis results showed that miR-937 expression was associated with lymph node metastasis and TNM stage. Patients with high miR-937 expression predicted a shorter overall survival rate. Functionally, overexpression of miR-937 promoted cell proliferation, migration, and invasion, while inhibition of miR-937 inhibited these cellular behaviors in vitro. Conclusions These results suggested that miR-937 may act as a prognostic biomarker and a potential target for therapeutic strategy, as well as promote proliferation, migration, and invasion of colon cancer.
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Affiliation(s)
- Huiya Liu
- Department of Gastroenterology, Heze Municipal Hospital, Heze, 274400, Shandong, China
| | - Lin Ma
- Department of Laboratory Medicine, Heze Municipal Hospital, Heze, 274400, Shandong, China
| | - Ling Wang
- Department of Cardiac Intervention, Heze Municipal Hospital, Heze, 274400, Shandong, China
| | - Yizuo Yang
- Department of Geriatrics, Heze Municipal Hospital, No. 2888, Caozhou Road, Heze, 274400, Shandong, China.
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