LncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox.

Abstract

Long noncoding RNAs (lncRNAs) are key regulators of hepatic stellate cells (HSCs), yet the role of upregulated lncRNA-NONRATT013819.2 in activated HSCs remains uncertain. In this study, the effects of NONRATT013819.2 on proliferation, apoptosis, migration, and contraction of transforming growth factor (TGF)-β1-induced HSCs were investigated. The mechanisms of NONRATT013819.2 on the activated HSCs were explored by loss-of-function of NONRATT013819.2 and gain-of-function of the target gene. Here, TGF-β1 treatment resulted in a gradual increase in the expression of cytoskeleton markers (collagen, α-SMA, and TIMP1), NONRATT013819.2, miR24-3p, and lysyl oxidase (Lox) over time in HSCs. NONRATT013819.2 acted as a sponge of miR24-3p to competitively abolish the inhibition of the lox gene in HSCs. Silencing of NONRATT013819.2 suppressed the expression of cytoskeleton markers, proliferation, and the proportion of cells that entered the S-phase, and promoted apoptosis in TGF-β1-activated HSCs. These effects were reversed when lox overexpression was introduced simultaneously. Similarly, silencing of NONRATT013819.2 also blocked ECM reconstruction, while recused by lox overexpression in TGF-β1-activated HSCs. In conclusion, upregulation of NONRATT013819.2 promotes the myofibroblastic transition by competitively binding miR24-3p to release lox in HSCs. Therefore, targeted therapy of NONRATT013819.2 may have the potential for liver fibrosis.