MiR-130b-3p Suppress the Migration, Proliferation and Chemosensitization of Hepatocellular Carcinoma Cells
DOI:
https://doi.org/10.30683/1929-2279.2024.13.04Keywords:
HCC, small RNA, non-coding RNA, HepG2, small RNAs, mir130bAbstract
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers globally, yet its pathogenesis remains incompletely understood. Among the various mechanisms contributing to HCC development, small RNAs, such as microRNAs (miRNAs), play a significant role. miRNAs are non-coding RNAs, typically 20-30 nucleotides long, that regulate gene transcription by binding to RNAs, affecting downstream signaling pathways. One such miRNA, hsa-miR-130b-3p, has been associated with cancer development, including HCC, although the full extent of its involvement remains unclear. This study aimed to explore the link between hsa-miR-130b-3p and HCC using bioinformatics analyses and in vitro assays. Publicly available databases were utilized for expression profiling, mRNA and lncRNA target prediction, pathway enrichment, and methylation analysis. In vitro experiments were conducted using a hsa-miR-130b-3p inhibitor in HepG2 cells to assess its effects on proliferation, migration, and oxaliplatin sensitivity. Our findings show that hsa-miR-130b-3p is upregulated in multiple cancers, including HCC, targeting cancer-related genes and interacting with various lncRNAs. Inhibition of hsa-miR-130b-3p reduced cancer cell proliferation and migration, while enhancing drug sensitivity to oxaliplatin. These results suggest that hsa-miR-130b-3p may play a role in HCC pathogenesis, but further studies are required to fully understand its mechanisms.
References
Lafaro KJ, Demirjian AN, Pawlik TM. Epidemiology of hepatocellular carcinoma. Surgical Oncology Clinics of North America 2015; 24(1): 1-17. https://doi.org/10.1016/j.soc.2014.09.001
Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. Journal of Hepatology 2020; 72(2): 250-61. https://doi.org/10.1016/j.jhep.2019.08.025
Teufel A, Kudo M, Qian Y, Daza J, Rodriguez I, Reissfelder C, et al. Current Trends and Advancements in the Management of Hepatocellular Carcinoma. Digestive Diseases 2024; 42(4): 349-60. https://doi.org/10.1159/000538815
O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in Endocrinology 2018; 9: 402. https://doi.org/10.3389/fendo.2018.00402
Broughton JP, Lovci MT, Huang JL, Yeo GW, Pasquinelli AE. Pairing beyond the Seed Supports MicroRNA Targeting Specificity. Molecular Cell 2016; 64(2): 320-33. https://doi.org/10.1016/j.molcel.2016.09.004
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduction and Targeted Therapy 2016; 1(1): 15004. https://doi.org/10.1038/sigtrans.2015.4
Onishi M, Ochiya T, Tanaka Y. MicroRNA and liver cancer. Cancer drug resistance (Alhambra, Calif) 2020; 3(3): 385-400. https://doi.org/10.20517/cdr.2019.110
Nagy Á, Lánczky A, Menyhárt O, Győrffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep 2018; 8(1): 9227. https://doi.org/10.1038/s41598-018-27521-y
Mou T, Zhu D, Wei X, Li T, Zheng D, Pu J, et al. Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis. World Journal of Surgical Oncology 2017; 15(1): 63. https://doi.org/10.1186/s12957-017-1127-2
Lou W, Liu J, Ding B, Chen D, Xu L, Ding J, et al. Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of HBV-related HCC. J Transl Med 2019; 17(1): 7. https://doi.org/10.1186/s12967-018-1761-7
Wang D, Song Q, Zhao T, Wang F, Yu Y, Qi J, et al. Long non-coding RNA MRPS30 divergent transcript can be detected in the cytoplasm of triple-negative breast cancer cells and is targeted by microRNA-130b. Bioengineered 2022; 13(3): 5954-61. https://doi.org/10.1080/21655979.2022.2031393
Gao Z, Wang N, Liu X. Human placenta mesenchymal stem cell-derived exosome shuttling microRNA-130b-3p from gestational diabetes mellitus patients targets ICAM-1 and perturbs human umbilical vein endothelial cell angiogenesis. Acta Diabetologica 2022; 59(8): 1091-107. https://doi.org/10.1007/s00592-022-01910-2
Kim Y, Kim H, Bang S, Jee S, Jang K. MicroRNA-130b functions as an oncogene and is a predictive marker of poor prognosis in lung adenocarcinoma. Laboratory Investigation; a Journal of Technical Methods and Pathology 2021; 101(2): 155-64. https://doi.org/10.1038/s41374-020-00496-z
Hashimoto Y, Shiina M, Dasgupta P, Kulkarni P, Kato T, Wong RK, et al. Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer. Cancer Prevention Research (Philadelphia, Pa) 2019; 12(9): 585-98. https://doi.org/10.1158/1940-6207.CAPR-18-0509
Liu CJ, Xie GY, Miao YR, Xia M, Wang Y, Lei Q, et al. EVAtlas: a comprehensive database for ncRNA expression in human extracellular vesicles. Nucleic Acids Res 2022; 50(D1): D111-d7. https://doi.org/10.1093/nar/gkab668
Pan CY, Lin WC. miR-TV: an interactive microRNA Target Viewer for microRNA and target gene expression interrogation for human cancer studies. Database: the Journal of Biological Databases and Curation 2020; 2020. https://doi.org/10.1093/database/baz148
Wang X. miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA (New York, NY) 2008; 14(6): 1012-7. https://doi.org/10.1261/rna.965408
Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28(1): 27-30. https://doi.org/10.1093/nar/28.1.27
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature Genetics 2000; 25(1): 25-9. https://doi.org/10.1038/75556
Elizarraras JM, Liao Y, Shi Z, Zhu Q, Pico Alexander R, Zhang B. WebGestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics. Nucleic Acids Research 2024; 52(W1): W415-W21. https://doi.org/10.1093/nar/gkae456
Zhou G, Soufan O, Ewald J, Hancock REW, Basu N, Xia J. NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Research 2019; 47(W1): W234-W41. https://doi.org/10.1093/nar/gkz240
Breuer K, Foroushani AK, Laird MR, Chen C, Sribnaia A, Lo R, et al. InnateDB: systems biology of innate immunity and beyond--recent updates and continuing curation. Nucleic Acids Res 2013; 41(Database issue): D1228-33. https://doi.org/10.1093/nar/gks1147
Miao Y-R, Liu W, Zhang Q, Guo A-Y. lncRNASNP2: an updated database of functional SNPs and mutations in human and mouse lncRNAs. Nucleic Acids Research 2018; 46(D1): D276-D80. https://doi.org/10.1093/nar/gkx1004
Gong J, Liu W, Zhang J, Miao X, Guo A-Y. lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse. Nucleic Acids Research 2015; 43(D1): D181-D6. https://doi.org/10.1093/nar/gku1000
Díez-Villanueva A, Mallona I, Peinado MA. Wanderer, an interactive viewer to explore DNA methylation and gene expression data in human cancer. Epigenetics & Chromatin 2015; 8(1): 22. https://doi.org/10.1186/s13072-015-0014-8
Liao Y, Wang C, Yang Z, Liu W, Yuan Y, Li K, et al. Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma. Theranostics 2020; 10(12): 5209-24. https://doi.org/10.7150/thno.43640
Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, et al. miR-130b Promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell 2010; 7(6): 694-707. https://doi.org/10.1016/j.stem.2010.11.010
Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open 2012; 2(2): e000825. https://doi.org/10.1136/bmjopen-2012-000825
Yan W, Wang Y, Chen Y, Guo Y, Li Q, Wei X. Exosomal miR-130b-3p Promotes Progression and Tubular Formation Through Targeting PTEN in Oral Squamous Cell Carcinoma. Frontiers in Cell and Developmental Biology 2021; 9: 616306. https://doi.org/10.3389/fcell.2021.616306
Miao Y, Zheng W, Li N, Su Z, Zhao L, Zhou H, et al. MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway. Scientific Reports 2017; 7(1): 41942. https://doi.org/10.1038/srep41942
Ahn S, Kwon A, Huh YH, Rhee S, Song WK. Tumor-derived miR-130b-3p induces cancer-associated fibroblast activation by targeting SPIN90 in luminal A breast cancer. Oncogenesis 2022; 11(1): 47. https://doi.org/10.1038/s41389-022-00422-6
Yang Z, Tang Y, Wu X, Wang J, Yao W. MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer. Biochemical Genetics 2024. https://doi.org/10.1007/s10528-024-10696-7
Lv M, Li X, Zheng C, Tian W, Yang H, Yin Z, et al. Exosomal miR-130b-3p suppresses metastasis of non-small cell lung cancer cells by targeting DEPDC1 via TGF-β signaling pathway. International Journal of Biological Macromolecules 2024; 275: 133594. https://doi.org/10.1016/j.ijbiomac.2024.133594
Li H, Liu P, Li D, Wang Z, Ding Z, Zhou M, et al. STAT3/miR-130b-3p/MBNL1 feedback loop regulated by mTORC1 signaling promotes angiogenesis and tumor growth. Journal of Experimental & Clinical Cancer Research 2022; 41(1): 297. https://doi.org/10.1186/s13046-022-02513-z
Ramalho-Carvalho J, Graça I, Gomez A, Oliveira J, Henrique R, Esteller M, et al. Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer. Journal of Hematology & Oncology 2017; 10(1): 43. https://doi.org/10.1186/s13045-017-0415-1
Chen P, Zeng Z, Wang J, Cao W, Song C, Lei S, et al. Long noncoding RNA LINC00857 promotes pancreatic cancer proliferation and metastasis by regulating the miR-130b/RHOA axis. Cell Death Discovery 2022; 8(1): 198. https://doi.org/10.1038/s41420-022-01008-2
Li C-X, Li H-G, Huang L-T, Kong Y-W, Chen F-Y, Liang J-Y, et al. H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p. Cell Death & Disease 2017; 8(11): e3174-e. https://doi.org/10.1038/cddis.2017.516
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.