LncRNA CCAT2, involving miR-34a/TGF-β1/Smad4 signaling, regulate hepatic stellate cells proliferation

• Published in: Scientific reports Vol. 12; no. 1; p. 21199
• Main Authors: Gao, Haibing, Wang, Xiangmei, Ma, Huaxi, Lin, Shenglong, Zhang, Dongqing, Wu, Wenjun, Liao, Ziyuan, Chen, Mengyun, Ye, Hanhui, Li, Qin, Lin, Minghua, Li, Dongliang
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.12.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Apoptosis; Cell proliferation; Cell Proliferation - genetics; Collagen; Extracellular matrix; Fibrosis; Flow cytometry; Hepatic Stellate Cells; Humans; Liver; Liver Cirrhosis - genetics; MicroRNAs - genetics; Non-coding RNA; Protein biosynthesis; Protein synthesis; RNA, Long Noncoding - genetics; Signal Transduction; Smad4 protein; Smad4 Protein - genetics; Stellate cells; Transfection; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-25738-6

miR-34a targeting on Smad4 plays important role in TGF-β1 pathway which is a dominant factor for balancing collagen production and degradation in hepatic stellate cells. TGF-β1/Smad4 regulated collagen deposition is a hallmark of hepatic fibrosis. The potential regulation on miR-34a by LncRNAs in hepatic stellate cells (HSCs) is still reserved to be revealed. In current study, it was hypothesized that a miR-34a interactor, lncRNA CCAT2 may regulate TGF-β1 pathway in liver fibrotic remodeling. The interaction between CCAT2 and miR-34a-5p was checked by dual luciferase assay. the effects of CCAT2 and miR-34a-5p on cell proliferation and apoptosis were verified by MTT assay, colony formation assay, and flow cytometry assay. Dual luciferase activity showed CCAT2 are targets of miR-34a-5p. Sh-CCAT2 transfection prohibit HSCs proliferation and induce HSCs apoptosis, also inhibited ECM protein synthesis in HSCs. Decreased miR-34a-5p enhanced HSCs proliferation, blocked HSCs apoptosis and promoted ECM protein production. miR-34a-5p inhibitor undo protective regulation of sh-CCAT2 in liver fibrosis. Furthermore, clinical investigation showed that CCAT2 and Smad4 expression level were significantly induced, while miR-34a-5p was significantly decreased in HBV related liver fibrosis serum. In conclusion, activated HSCs via TGF-β1/Smad4 signaling pathway was successfully alleviated by CCAT2 inhibition through miR-34a-5p elevation.