Articles
6 May 2025
Vol. 69 No. 2 (2025)
MiR-122-5p inhibits the epithelial mesenchymal transition of liver cancer cells by inducing hiPSCs to differentiate into hepatocyte-like cells
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Epithelial-mesenchymal transition (EMT) is closely linked to liver cancer prognosis, invasiveness, and aggressiveness. One promising treatment for liver cancer is cell therapy, where stem cells are stimulated to develop into functional liver cells. This study aimed to investigate the effect of miR-122-5p on the differentiation of human induced pluripotent stem cells (hiPSCs) into hepatocyte-like cells and its impact on the EMT process in liver cancer cells. MiR-122-5p was overexpressed or silenced in hiPSCs to analyze the expression of liver-specific markers, including AFP, ALB and ASGPR, to confirm hepatocyte-like differentiation. A co-culture system with HepG2 liver cancer cells was also used to evaluate the effect of miR-122-5p-overexpressing hiPSCs or miR-122-5p-silencing hiPSCs on the expression of EMT markers. Results revealed that overexpression of miR-122-5p in hiPSCs induced hepatocyte-like characteristics, as evidenced by increased levels of AFP, ALB, and ASGPR. However, knockdown of miR-122-5p had the opposite effect. In the co-culture system, hiPSCs overexpressing miR-122-5p inhibited the EMT process of HepG2 cells, resulting in increased levels of mesenchymal markers and decreased levels of epithelial markers. Taken together, miR-122-5p promotes the differentiation of hiPSCs into hepatocyte-like cells and inhibits EMT process of liver cancer cells. Targeting miR-122-5p may be a novel approach to prevent liver cancer progression through cell therapy.
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1. Song C, Lv J, Yu C, Zhu M, Yu C, Guo Y, et al. Adherence to healthy lifestyle and liver cancer in Chinese: a prospective cohort study of 0.5 million people. Brit J Cancer 2022;126:815-21. DOI: https://doi.org/10.1038/s41416-021-01645-x
2. Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer 2020;1873:188314. DOI: https://doi.org/10.1016/j.bbcan.2019.188314
3. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019;20:69-84. DOI: https://doi.org/10.1038/s41580-018-0080-4
4. Yoshida GJ. Emerging role of epithelial-mesenchymal transition in hepatic cancer. J Exp Clin Canc Res 2016;35:141. DOI: https://doi.org/10.1186/s13046-016-0419-7
5. Peng WC, Kraaier LJ, Kluiver TA. Hepatocyte organoids and cell transplantation: What the future holds. Exp Mol Med 2021;53:1512-28. DOI: https://doi.org/10.1038/s12276-021-00579-x
6. Rountree CB, Mishra L, Willenbring H. Stem cells in liver diseases and cancer: recent advances on the path to new therapies. Hepatology 2012;55:298-306. DOI: https://doi.org/10.1002/hep.24762
7. Aboul-Soud M, Alzahrani AJ, Mahmoud A. Induced pluripotent stem cells (iPSCs)-roles in regenerative therapies, disease modelling and drug screening. Cells 2021;10:2319. DOI: https://doi.org/10.3390/cells10092319
8. Poetsch MS, Strano A, Guan K. Human induced pluripotent stem cells: from cell origin, genomic stability, and epigenetic memory to translational medicine. Stem Cells 2022;40:546-55. DOI: https://doi.org/10.1093/stmcls/sxac020
9. Xing Q, Luo Y, Gao Y, Zhang S, Zhu Z, Wang Y, et al. Hepatectomised patient sera promote hepatocyte differentiation of human-induced pluripotent stem cells. Digest Liver Dis 2014;46:731-7. DOI: https://doi.org/10.1016/j.dld.2014.04.013
10. Yuan L, Zhang Y, Liu X, Chen Y, Zhang L, Cao J, et al. Agonist c-Met monoclonal antibody augments the proliferation of hiPSC-derived hepatocyte-like cells and improves cell transplantation therapy for liver failure in mice. Theranostics 2019;9:2115-28. DOI: https://doi.org/10.7150/thno.30009
11. Alexanova A, Raitoharju E, Valtonen J, Aalto-Setala K, Viiri LE. Coronary artery disease patient-derived iPSC-hepatocytes have distinct miRNA profile that may alter lipid metabolism. Sci Rep-Uk 2023;13:1706. DOI: https://doi.org/10.1038/s41598-023-28981-7
12. Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 2017;16:203-22. DOI: https://doi.org/10.1038/nrd.2016.246
13. Ghafouri-Fard S, Honarmand TK, Hussen BM, Taheri M. MicroRNA signature in liver cancer. Pathol Res Pract 2021;219:153369. DOI: https://doi.org/10.1016/j.prp.2021.153369
14. Roa-Colomo A, Lopez GM, Molina-Vallejo P, Rojas A, Sanchez MG, Aranda-Garcia V, et al. Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception. Front Mol Biosci 2022;9:1074277. DOI: https://doi.org/10.3389/fmolb.2022.1074277
15. Tao L, Wang Y, Shen Z, Cai J, Zheng J, Xia S, et al. Activation of IGFBP4 via unconventional mechanism of miRNA attenuates metastasis of intrahepatic cholangiocarcinoma. Hepatol Int 2024;18:91-107. DOI: https://doi.org/10.1007/s12072-023-10552-7
16. Guo L, Wang Z, Fu Y, Wu S, Zhu Y, Yuan J, et al. MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma. Sci Rep 2024;14:10019. DOI: https://doi.org/10.1038/s41598-024-59080-w
17. Li Y, Lu L, Cai X. Liver Regeneration and cell transplantation for end-stage liver disease. Biomolecules 2021;11:1907. DOI: https://doi.org/10.3390/biom11121907
18. Hu C, Zhao L, Wu Z, Li L. Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury. Stem Cell Res Ther 2020;11:88. DOI: https://doi.org/10.1186/s13287-020-01596-9
19. Kakinuma S, Nakauchi H, Watanabe M. Hepatic stem/progenitor cells and stem-cell transplantation for the treatment of liver disease. J Gastroenterol 2009;44:167-72. DOI: https://doi.org/10.1007/s00535-008-2297-z
20. Dianat N, Steichen C, Vallier L, Weber A, Dubart-Kupperschmitt A. Human pluripotent stem cells for modelling human liver diseases and cell therapy. Curr Gene Ther 2013;13:120-32. DOI: https://doi.org/10.2174/1566523211313020006
21. Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, et al. Induced pluripotent stem cells and their use in human models of disease and development. Physiol Rev 2019;99:79-114. DOI: https://doi.org/10.1152/physrev.00039.2017
22. Ding Y, Yuan X, Zou Y, Gao J, Xu X, Sun H, et al. OCT4, SOX2 and NANOG co-regulate glycolysis and participate in somatic induced reprogramming. Cytotechnology 2022;74:371-83. DOI: https://doi.org/10.1007/s10616-022-00530-6
23. Xia M, Chen J, Hu Y, Qu B, Bu Q, Shen H. miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2. Cancer Biol Ther 2024;25:2315651. DOI: https://doi.org/10.1080/15384047.2024.2315651
24. Olarewaju O, Hu Y, Tsay HC, Yuan Q, Eimterbäumer S, Xie Y, et al. MicroRNA miR-20a-5p targets CYCS to inhibit apoptosis in hepatocellular carcinoma. Cell Death Dis 2024;15:456. DOI: https://doi.org/10.1038/s41419-024-06841-0
25. Sun X, Ding W, Jiang C, Fang Z. MiR-557 suppresses hepatocellular carcinoma cell proliferation and migration via downregulating CBX4. BIOCELL. 2024;48:1071-9. DOI: https://doi.org/10.32604/biocell.2024.050519
26. Yang D, Zhang P, Yang Z, Hou G, Yang Z. miR-4461 inhibits liver cancer stem cells expansion and chemoresistance via regulating SIRT1. Carcinogenesis 2024 45:463-74. DOI: https://doi.org/10.1093/carcin/bgac093
27. Salloum-Asfar S, Abdulla SA, Taha RZ, Thompson IR, Emara MM. Combined noncoding RNA-mRNA regulomics signature in reprogramming and pluripotency in iPSCs. Cells 2022;11:3833. DOI: https://doi.org/10.3390/cells11233833
28. Li F, Wei H, Jin Y, Xue T, Xu Y, Wang H, et al. Microfluidic fabrication of microRNA-induced hepatocyte-like cells/human umbilical vein endothelial cells-laden microgels for acute liver failure treatment. Acs Nano 2023;17:25243-56. DOI: https://doi.org/10.1021/acsnano.3c08495
29. Yoshimoto K, Maki K, Adachi T, Kamei KI. Cyclic stretching enhances angiocrine signals at liver bud stage from human pluripotent stem cells in two-dimensional culture. Tissue Eng Pt A 2024;30:426-39. DOI: https://doi.org/10.1089/ten.tea.2023.0148
30. Davis FM, Stewart TA, Thompson EW, Monteith GR. Targeting EMT in cancer: opportunities for pharmacological intervention. Trends Pharmacol Sci 2014;35:479-88. DOI: https://doi.org/10.1016/j.tips.2014.06.006
31. Sabouni E, Nejad MM, Mojtabavi S, Khoshduz S, Mojtabavi M, Nadafzadeh N, et al. Unraveling the function of epithelial-mesenchymal transition (EMT) in colorectal cancer: Metastasis, therapy response, and revisiting molecular pathways. Biomed Pharmacother 2023;160:114395. DOI: https://doi.org/10.1016/j.biopha.2023.114395
32. Mong EF, Yang Y, Akat KM, Canfield J, VanWye J, Lockhart J, et al. Chromosome 19 microRNA cluster enhances cell reprogramming by inhibiting epithelial-to-mesenchymal transition. Sci Rep-Uk 2020;10:3029. DOI: https://doi.org/10.1038/s41598-020-59812-8
33. Unternaehrer JJ, Zhao R, Kim K, Cesana M, Powers JT, Ratanasirintrawoot S, et al. The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming. Stem Cell Rep 2014;3:691-8. DOI: https://doi.org/10.1016/j.stemcr.2014.09.008
34. Dong H, Yin C, Xiao D, Tang Y. Identification of differentially expressed genes to predict the risk of heart failure in older patients with hypertrophic cardiomyopathy. Aging (Albany NY) 2024;16:10860-7. DOI: https://doi.org/10.18632/aging.205956
35. Yu Z, Song L, Wang Y, Chen X, Chen P, Zhong S, et al. Integrating bulk-RNA and single-cell analysis reveals heterogeneous expression of cuproptosis-related sorafenib-resistant genes in hepatocellular carcinoma. Oncologie 2024;26: 783-97. DOI: https://doi.org/10.1515/oncologie-2024-0175
36. Sensi B, Angelico R, Toti L, Conte L, Coppola A, Tisone G, et al. Mechanism, potential, and concerns of immunotherapy for hepatocellular carcinoma and liver transplantation. Curr Mol Pharmacol 2024;17:e18761429310703. DOI: https://doi.org/10.2174/0118761429310703240823045808
Supporting Agencies
this study was supported by the Tianjin Health Bureau Funded ProjectHow to Cite
MiR-122-5p inhibits the epithelial mesenchymal transition of liver cancer cells by inducing hiPSCs to differentiate into hepatocyte-like cells. (2025). European Journal of Histochemistry, 69(2). https://doi.org/10.4081/ejh.2025.4190
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