Acknowledgement
The project was supported by the National Natural Science Foundation of China (No. 81873576), Wenzhou Municipal Science and technology Bureau (No. Y20220023) and the project of Wenzhou Medical University Basic Scientific Research (No. KYYW201904).
References
- Parola M, Pinzani M. Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med 2019;65:37-55. https://doi.org/10.1016/j.mam.2018.09.002
- Mittermeier C, Konopa A, Muehlich S. Molecular mechanisms to target cellular senescence in hepatocellular carcinoma. Cells 2020;9(12).
- Higashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 2017;121:27-42. https://doi.org/10.1016/j.addr.2017.05.007
- Hirata H, Hinoda Y, Ueno K, Shahryari V, Tabatabai ZL, Dahiya R. MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer. Carcinogenesis 2012;33(1):41-8. https://doi.org/10.1093/carcin/bgr239
- Liang Z, Xu J, Ma Z, Li G, Zhu W. MiR-187 suppresses non-small-cell lung cancer cell proliferation by targeting FGF9. Bioengineered 2020;11(1):70-80. https://doi.org/10.1080/21655979.2019.1706287
- Jing L, Li H, Zhang T, Lu J, Zhong L. MicroRNA4530 suppresses cell proliferation and induces apoptosis by targeting RASA1 in human umbilical vein endothelial cells. Mol Med Rep 2019;19(5):3393-402. https://doi.org/10.3892/mmr.2019.10000
- Li T, Zhou W, Li Y, Gan Y, Peng Y, Xiao Q, Ouyang C, Wu A, Zhang S, Liu J, et al. MiR-4524b-5p/WTX/beta-catenin axis functions as a regulator of metastasis in cervical cancer. PLoS One 2019;14(4):e0214822.
- Chen J, Yu Y, Li S, Liu Y, Zhou S, Cao S, Yin J, Li G. MicroRNA-30a ameliorates hepatic fibrosis by inhibiting Beclin1-mediated autophagy. J Cell Mol Med 2017;21(12):3679-92. https://doi.org/10.1111/jcmm.13278
- Caviglia JM, Yan J, Jang MK, Gwak GY, Affo S, Yu L, Olinga P, Friedman RA, Chen X, Schwabe RF. MicroRNA-21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis. Hepatology 2018;67(6):2414-29. https://doi.org/10.1002/hep.29627
- Markovic J, Sharma AD, Balakrishnan A. MicroRNA-221: a fine tuner and potential biomarker of chronic liver injury. Cells 2020;9(8).
- Yu F, Lu Z, Chen B, Wu X, Dong P, Zheng J. Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation. J Cell Mol Med 2015;19(11):2617-32. https://doi.org/10.1111/jcmm.12655
- Wu K, Ye C, Lin L, Chu Y, Ji M, Dai W, Zeng X, Lin Y. Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT. Clin Sci (Lond) 2016;130(16):1469-80. https://doi.org/10.1042/CS20160334
- Gao Y, Li J, Wang J, Li X, Li J, Chu S, Li L, Chen N, Zhang L. Ginsenoside Rg1 prevent and treat inflammatory diseases: a review. Int Immunopharmacol 2020;87:106805.
- Korivi M, Hou CW, Huang CY, Lee SD, Hsu MF, Yu SH, Chen CY, Liu YY, Kuo CH. Ginsenoside-Rg1 protects the liver against exhaustive exercise-induced oxidative stress in rats. Evid Based Complement Alternat Med 2012:932165. 2012.
- Mo C, Xie S, Zeng T, Lai Y, Huang S, Zhou C, Yan W, Huang S, Gao L, Lv Z. Ginsenoside-Rg1 acts as an IDO1 inhibitor, protects against liver fibrosis via alleviating IDO1-mediated the inhibition of DCs maturation. Phytomedicine 2021;84:153524.
- Lee SJ, Kim SJ, Lee HS, Kwon OS. PKCdelta mediates NF-kappaB inflammatory response and downregulates SIRT1 expression in liver fibrosis. Int J Mol Sci 2019;20(18).
- Chang W, Yang M, Song L, Shen K, Wang H, Gao X, Li M, Niu W, Qin X. Isolation and culture of hepatic stellate cells from mouse liver. Acta Biochim Biophys Sin (Shanghai) 2014;46(4):291-8. https://doi.org/10.1093/abbs/gmt143
- Gravett AM, Dalgleish AG, Copier J. In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells. Sci Rep 2019;9(1):1544.
- Veland N, Hardikar S, Zhong Y, Gayatri S, Dan J, Strahl BD, Rothbart SB, Bedford MT, Chen T. The arginine methyltransferase PRMT6 regulates DNA methylation and contributes to global DNA hypomethylation in cancer. Cell Rep 2017;21(12):3390-7. https://doi.org/10.1016/j.celrep.2017.11.082
- Yu F, Chen B, Dong P, Zheng J. HOTAIR epigenetically modulates PTEN expression via MicroRNA-29b: a novel mechanism in regulation of liver fibrosis. Mol Ther 2017;25(1):205-17. https://doi.org/10.1016/j.ymthe.2016.10.015
- Dituri F, Mancarella S, Cigliano A, Chieti A, Giannelli G. TGF-Beta as multifaceted orchestrator in HCC progression: signaling, EMT, immune microenvironment, and novel therapeutic perspectives. Semin Liver Dis 2019;39(1):53-69. https://doi.org/10.1055/s-0038-1676121
- Brockhausen J, Tay SS, Grzelak CA, Bertolino P, Bowen DG, d'Avigdor WM, Teoh N, Pok S, Shackel N, Gamble JR, et al. miR-181a mediates TGF-beta-induced hepatocyte EMT and is dysregulated in cirrhosis and hepatocellular cancer. Liver Int 2015;35(1):240-53. https://doi.org/10.1111/liv.12517
- Miyazawa K, Miyazono K. Regulation of TGF-beta family signaling by inhibitory smads. Cold Spring Harb Perspect Biol 2017;9(3).
- Kit Leng Lui S, Iyengar PV, Jaynes P, Isa Z, Pang B, Tan TZ, Eichhorn PJA. USP26 regulates TGF-beta signaling by deubiquitinating and stabilizing SMAD7. EMBO Rep 2017;18(5):797-808. https://doi.org/10.15252/embr.201643270
- Yang Q, Chen HY, Wang JN, Han HQ, Jiang L, Wu WF, Wei B, Gao L, Ma QY, Liu XQ, et al. Alcohol promotes renal fibrosis by activating Nox2/4-mediated DNA methylation of Smad7. Clin Sci (Lond) 2020;134(2):103-22. https://doi.org/10.1042/CS20191047
- Bian EB, Huang C, Wang H, Chen XX, Zhang L, Lv XW, Li J. Repression of Smad7 mediated by DNMT1 determines hepatic stellate cell activation and liver fibrosis in rats. Toxicol Lett 2014;224(2):175-85. https://doi.org/10.1016/j.toxlet.2013.10.038
- Xue LP, Fu XL, Hu M, Zhang LW, Li YD, Peng YL, Ding P. Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway. Biochem Biophys Res Commun 2018;501(4):827-32. https://doi.org/10.1016/j.bbrc.2018.04.055
- Du N, Xu Z, Gao M, Liu P, Sun B, Cao X. Combination of Ginsenoside Rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-beta1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy. Drug Des Devel Ther 2018;12:3517-24. https://doi.org/10.2147/DDDT.S171286
- Wei X, Chen Y, Huang W. Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo. Biofactors 2018;44(4):327-35. https://doi.org/10.1002/biof.1432
- Nieto MA, Huang RY, Jackson RA, Thiery JP. Emt: 2016. Cell 2016;166(1):21-45. https://doi.org/10.1016/j.cell.2016.06.028
- Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol 2019;29(3):212-26. https://doi.org/10.1016/j.tcb.2018.12.001
- Choi SS, Syn WK, Karaca GF, Omenetti A, Moylan CA, Witek RP, Agboola KM, Jung Y, Michelotti GA, Diehl AM. Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway. J Biol Chem 2010;285(47):36551-60. https://doi.org/10.1074/jbc.M110.168542
- Giannelli G, Koudelkova P, Dituri F, Mikulits W. Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol 2016;65(4): 798-808. https://doi.org/10.1016/j.jhep.2016.05.007
- Su J, Morgani SM, David CJ, Wang Q, Er EE, Huang YH, Basnet H, Zou Y, Shu W, Soni RK, et al. TGF-beta orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1. Nature 2020;577(7791):566-71. https://doi.org/10.1038/s41586-019-1897-5
- Li SJ, Wang L, Sun ZX, Sun SJ, Gao J, Ma RL. LncRNA SNHG1 promotes liver cancer development through inhibiting p53 expression via binding to DNMT1. Eur Rev Med Pharmacol Sci 2019;23(7):2768-76.
- Yang JJ, Tao H, Huang C, Shi KH, Ma TT, Bian EB, Zhang L, Liu LP, Hu W, Lv XW, et al. DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis. Cell Signal 2013;25(5):1202-11. https://doi.org/10.1016/j.cellsig.2013.01.005
- Bian EB, Huang C, Ma TT, Tao H, Zhang H, Cheng C, Lv XW, Li J. DNMT1-mediated PTEN hypermethylation confers hepatic stellate cell activation and liver fibrogenesis in rats. Toxicol Appl Pharmacol 2012;264(1):13-22. https://doi.org/10.1016/j.taap.2012.06.022
- Ghazanchaei A, Mansoori B, Mohammadi A, Biglari A, Baradaran B. Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer. J Cell Physiol 2018;234(1):769-76. https://doi.org/10.1002/jcp.26891
- Friedrich M, Pracht K, Mashreghi MF, Jack HM, Radbruch A, Seliger B. The role of the miR-148/-152 family in physiology and disease. Eur J Immunol 2017;47(12):2026-38. https://doi.org/10.1002/eji.201747132
- Li L, Zhang L, Zhao X, Cao J, Li J, Chu G. Downregulation of miR-152 contributes to the progression of liver fibrosis via targeting Gli3 in vivo and in vitro. Exp Ther Med 2019;18(1):425-34. https://doi.org/10.3892/etm.2019.7595