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

Zhiwei Liang, Jian Li, Longshuan Zhao, Yilei Deng

Molecular medicine reports 2021 Mar

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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.

Citation

Zhiwei Liang, Jian Li, Longshuan Zhao, Yilei Deng. miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition. Molecular medicine reports. 2021 Mar;23(3)