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

Abstract

AbstractmiR-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.

lncRNA CCAT2 Protects Against Cardiomyocyte Injury After Myocardial Ischemia/Reperfusion by Regulating BMI1 Expression

“…35) Beyond this tumor-promoting role, CCAT2 can also regulate hepatic stellate cell proliferation and apoptosis. 36) Huang et al found that the detection of CCAT2 levels in patient serum could be used to predict the rupture of atherosclerotic plaques. 20) It also suggests that CCAT2 is associated with cardiovascular disorders.…”

Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage

“…Exosomal miR-210 uptake from ECs promotes angiogenesis by targeting specific processes depending on the tumor microenvironment [ 100 ]. The chromatin epigenetic regulation of proangiogenic genes has also been attributed to different lncRNA packaged in EVs, although the mechanism is not fully elucidated [ 101 , 102 , 103 ] ( Figure 2 ). LncRNAs can work as molecular scaffold, assembling several chromatin regulator proteins and reshaping the DNA structure in the nucleus and thus favoring the transcription or silencing of target genes [ 104 ].…”