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miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition

  • Authors:
    • Zhiwei Liang
    • Jian Li
    • Longshuan Zhao
    • Yilei Deng
  • View Affiliations / Copyright

    Affiliations: Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
    Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 182
    |
    Published online on: December 31, 2020
       https://doi.org/10.3892/mmr.2020.11821
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Abstract

MicroRNAs (miRNAs/miRs) are a class of non‑coding RNAs that serve crucial roles in liver cancer and other liver injury diseases. However, the expression profile and mechanisms underlying miRNAs in liver fibrosis are not completely understood. The present study identified the novel miR‑375/Rac family small GTPase 1 (RAC1) regulatory axis in liver fibrosis. Reverse transcription‑quantitative PCR was performed to detect miR‑375 expression levels. MTT, flow cytometry and western blotting were performed to explore the in vitro roles of miR‑375. The dual‑luciferase reporter gene assay was performed to determine the potential mechanism underlying miR‑375 in liver fibrosis. miR‑375 expression was significantly downregulated in liver fibrosis tissues and cells compared with healthy control tissues and hepatocytes, respectively. Compared with the pre‑negative control group, miR‑375 overexpression inhibited mouse hepatic stellate cell (HSC) viability and epithelial‑mesenchymal transition, and alleviated liver fibrosis. The dual‑luciferase reporter assay results demonstrated that miR‑375 bound to RAC1. Moreover, the results indicated that miR‑375 regulated the hedgehog signaling pathway via RAC1 to restrain HSC viability and EMT, thus exerting its anti‑liver fibrosis function. The present study identified the miR‑375/RAC1 axis as a novel regulatory axis associated with the development of liver fibrosis.
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1 

Breitkopf-Heinlein K, Meyer C, König C, Gaitantzi H, Addante A, Thomas M, Wiercinska E, Cai C, Li Q, Wan F, et al: BMP-9 interferes with liver regeneration and promotes liver fibrosis. Gut. 66:939–954. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Hernandez-Gea V and Friedman SL: Pathogenesis of liver fibrosis. Annu Rev Pathol. 6:425–456. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Li W, Zhou C, Fu Y, Chen T, Liu X, Zhang Z and Gong T: Targeted delivery of hyaluronic acid nanomicelles to hepatic stellate cells in hepatic fibrosis rats. Acta Pharm Sin B. 10:693–710. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Yu F, Geng W, Dong P, Huang Z and Zheng J: LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212. Cell Death Dis. 9:10142018. View Article : Google Scholar : PubMed/NCBI

5 

Choi SS, Syn WK, Karaca GF, Omenetti A, Moylan CA, Witek RP, Agboola KM, Jung Y, Michelotti GA and Diehl AM: Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway. J Biol Chem. 285:36551–36560. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Yu F, Zheng Y, Hong W, Chen B, Dong P and Zheng J: MicroRNA-200a suppresses epithelial-to-mesenchymal transition in rat hepatic stellate cells via GLI family zinc finger 2. Mol Med Rep. 12:8121–8128. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Yu F, Lu Z, Chen B, Wu X, Dong P and Zheng J: Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation. J Cell Mol Med. 19:2617–2632. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Wang C, Luo J, Chen Z, Ye M, Hong Y, Liu J, Nie J, Zhao Q and Chang Y: MiR-375 impairs the invasive capabilities of hepatoma cells by targeting HIF1α under hypoxia. Dig Dis Sci. Mar 25–2020.(Epub ahead of print). doi: 10.1007/s10620-020-06202-9. View Article : Google Scholar

10 

Yang YZ, Zhao XJ, Xu HJ, Wang SC, Pan Y, Wang SJ, Xu Q, Jiao RQ, Gu HM and Kong LD: Magnesium isoglycyrrhizinate ameliorates high fructose-induced liver fibrosis in rat by increasing miR-375-3p to suppress JAK2/STAT3 pathway and TGF-β1/Smad signaling. Acta Pharmacol Sin. 40:879–894. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Ungefroren H, Witte D and Lehnert H: The role of small GTPases of the Rho/Rac family in TGF-β-induced EMT and cell motility in cancer. Dev Dyn. 247:451–461. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Choi SS, Sicklick JK, Ma Q, Yang L, Huang J, Qi Y, Chen W, Li YX, Goldschmidt-Clermont PJ and Diehl AM: Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology. 44:1267–1277. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Choi SS, Witek RP, Yang L, Omenetti A, Syn WK, Moylan CA, Jung Y, Karaca GF, Teaberry VS, Pereira TA, et al: Activation of Rac1 promotes hedgehog-mediated acquisition of the myofibroblastic phenotype in rat and human hepatic stellate cells. Hepatology. 52:278–290. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Ge B, Wu H, Shao D, Li S and Li F: Interfering with miR-24 alleviates rotenone-induced dopaminergic neuron injury via enhancing autophagy by up-regulating DJ-1. Aging Pathobiol Ther. 1:17–24. 2019. View Article : Google Scholar

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Yu F, Chen B, Dong P and Zheng J: HOTAIR epigenetically modulates PTEN expression via MicroRNA-29b: A novel mechanism in regulation of liver fibrosis. Mol Ther. 25:205–217. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Zhou X, Xiong J, Lu S, Luo L, Chen ZL, Yang F, Jin F, Wang Y, Ma Q, Luo YY, et al: Inhibitory effect of corilagin on miR-21-regulated hepatic fibrosis signaling pathway. Am J Chin Med. 47:1541–1569. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Wu JC, Chen R, Luo X, Li ZH, Luo SZ and Xu MY: MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2. World J Gastroenterol. 25:4468–4480. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Li BB, Li DL, Chen C, Liu BH, Xia CY, Wu HJ, Wu CQ, Ji GQ, Liu S, Ni W, et al: Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis. Sci Rep. 6:341572016. View Article : Google Scholar : PubMed/NCBI

20 

Wei S, Wang Q, Zhou H, Qiu J, Li C, Shi C, Zhou S, Liu R and Lu L: miR-455-3p alleviates hepatic stellate cell activation and liver fibrosis by suppressing HSF1 expression. Mol Ther Nucleic Acids. 16:758–769. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Yang L, Dong C, Yang J, Yang L, Chang N, Qi C and Li L: MicroRNA-26b-5p inhibits mouse liver fibrogenesis and angiogenesis by targeting PDGF receptor-beta. Mol Ther Nucleic Acids. 16:206–217. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Zou Y, Li S, Li Z, Song D, Zhang S and Yao Q: MiR-146a attenuates liver fibrosis by inhibiting transforming growth factor-β1 mediated epithelial-mesenchymal transition in hepatocytes. Cell Signal. 58:1–8. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Kikuchi M, Sekiya M, Hara N, Miyashita A, Kuwano R, Ikeuchi T, Iijima KM and Nakaya A: Disruption of a RAC1-centred network is associated with Alzheimer's disease pathology and causes age-dependent neurodegeneration. Hum Mol Genet. 29:817–833. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Kai Y, Kon R, Ikarashi N, Chiba Y, Kamei J and Sakai H: Role of Rac1 in augmented endothelin-1-induced bronchial contraction in airway hyperresponsive mice. J Pharmacol Sci. 141:106–110. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Bopp A, Wartlick F, Henninger C, Kaina B and Fritz G: Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging. Cell Death Dis. 4:e5582013. View Article : Google Scholar : PubMed/NCBI

26 

Venugopal SK, Jiang J, Kim TH, Li Y, Wang SS, Torok NJ, Wu J and Zern MA: Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am J Physiol Gastrointest Liver Physiol. 298:G101–G106. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liang Z, Li J, Zhao L and Deng Y: miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition. Mol Med Rep 23: 182, 2021.
APA
Liang, Z., Li, J., Zhao, L., & Deng, Y. (2021). miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition. Molecular Medicine Reports, 23, 182. https://doi.org/10.3892/mmr.2020.11821
MLA
Liang, Z., Li, J., Zhao, L., Deng, Y."miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition". Molecular Medicine Reports 23.3 (2021): 182.
Chicago
Liang, Z., Li, J., Zhao, L., Deng, Y."miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition". Molecular Medicine Reports 23, no. 3 (2021): 182. https://doi.org/10.3892/mmr.2020.11821
Copy and paste a formatted citation
x
Spandidos Publications style
Liang Z, Li J, Zhao L and Deng Y: miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition. Mol Med Rep 23: 182, 2021.
APA
Liang, Z., Li, J., Zhao, L., & Deng, Y. (2021). miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition. Molecular Medicine Reports, 23, 182. https://doi.org/10.3892/mmr.2020.11821
MLA
Liang, Z., Li, J., Zhao, L., Deng, Y."miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition". Molecular Medicine Reports 23.3 (2021): 182.
Chicago
Liang, Z., Li, J., Zhao, L., Deng, Y."miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition". Molecular Medicine Reports 23, no. 3 (2021): 182. https://doi.org/10.3892/mmr.2020.11821
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