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

Abstract

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.

• Authors: Haibing Gao, Xiangmei Wang, Huaxi Ma, Shenglong Lin, Dongqing Zhang, Wenjun Wu, Ziyuan Liao, Mengyun Chen, Hanhui Ye, Qin Li, Minghua Lin, Dongliang Li
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 21199 (12 08 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 36482069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Collagen
• MicroRNAs
• RNA, Long Noncoding
• Smad4 Protein
• SMAD4 protein, human
• Transforming Growth Factor beta1
• TGFB1 protein, human

Topics

• Humans
• Cell Proliferation (genetics)
• Collagen
• Hepatic Stellate Cells
• Liver Cirrhosis (genetics)
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)
• Signal Transduction
• Smad4 Protein (genetics)
• Transforming Growth Factor beta1 (genetics)