Downregulated long non-coding RNA LINC01093 in liver fibrosis promotes hepatocyte apoptosis via increasing ubiquitination of SIRT1. (11th February 2020)

• Record Type: Journal Article
• Authors: Tang, Yinhe; Ma, Naijing; Luo, Hao; Chen, Shizuan; Yu, Fuxiang
• Is Part Of: Journal of biochemistry. Volume 167:Number 5(2020)
• Page Start: 525
• Page End: 534
• Publication Date: 2020-02-11
• Subjects: apoptosis -- hepatocyte -- liver fibrosis -- lncRNA LINC01093 -- ubiquitination; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Electronic journals; 572.05
• DOI: 10.1093/jb/mvaa013
• Languages: English
• ISSNs: 0021-924X

Abstract

Abstract: The apoptosis of hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thus promoting the accumulation of extracellular matrix proteins and aggravating liver fibrosis. Silent information regulator 1 (SIRT1) is an anti-fibrotic protein whose downregulation induces hepatocyte apoptosis. This study aims to identify whether SIRT1 is regulated by long non-coding RNA LINC01093 and explore its underlying mechanisms. Liver fibrosis was induced in mice using CCl4, and the differential expressions of several fibrosis-related long noncoding RNAs were detected in liver tissues. The effect of LINC01093 on cell apoptosis and viability of hepatocytes were investigated after LINC01093 overexpression or knockdown using flow cytometry and MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay. The anti-fibrotic effect of LINC01093 overexpression was observed in vivo . LncRNA LINC01093 is downregulated in CCl4 -induced liver tissues and TGF-β1-stimulated hepatocytes. Downregulated LINC01093 promoted cell apoptosis and inhibited cell viability of hepatocytes. The co-culture between LINC01093-knockdown hepatocytes and HSCs increased the expressions of pro-fibrotic proteins. Downregulated LINC01093 promoted hepatocyte apoptosis via promoting degradation and ubiquitination of SIRT1 under TGF-β1 stimulation. The injection of LINC01093-overexpressing vectors alleviated liver fibrosis in vivo . In liver fibrosis, the downregulated LINC01093 promoted hepatocyte apoptosis, which is mediated by increasing the degradation and ubiquitination of SIRT1.