Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2020.11821. Epub 2021 Jan 5.
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.
微小 RNA（miRNA/miRs）是一类非编码 RNA，在肝癌和其他肝损伤疾病中发挥重要作用。然而，miRNA 在肝纤维化中的表达谱和作用机制尚不完全清楚。本研究在肝纤维化中鉴定了新的 miR-375/Rac 家族小 GTP 酶 1（RAC1）调控轴。采用逆转录定量 PCR 检测 miR-375 表达水平。通过 MTT、流式细胞术和 Western blot 检测 miR-375 在体外的作用。采用双荧光素酶报告基因检测 miR-375 在肝纤维化中的潜在作用机制。与健康对照组织和肝细胞相比，肝纤维化组织和细胞中 miR-375 的表达水平明显下调。与阴性对照前组相比，miR-375 过表达抑制了小鼠肝星状细胞（HSC）的活力和上皮-间充质转化，并减轻了肝纤维化。双荧光素酶报告基因检测结果表明，miR-375 与 RAC1 结合。此外，结果表明 miR-375 通过 RAC1 调控 hedgehog 信号通路，抑制 HSC 活力和 EMT，从而发挥其抗肝纤维化功能。本研究鉴定了 miR-375/RAC1 轴作为与肝纤维化发展相关的新的调控轴。
