LncRNA Neat1 expedites the progression of liver fibrosis in mice through targeting miR-148a-3p and miR-22-3p to upregulate <i>Cyth3</i>
Wei Huang, Feizhou Huang, Rui Zhang, Hongwu Luo
Abstract
Liver fibrosis is a common response to chronic liver injury, ultimately leading to cirrhosis. The activation of hepatic stellate cells (HSCs) plays a dominant role in liver fibrosis. The regulatory roles of long noncoding RNAs (lncRNAs) in multiple human diseases have been observed. This study was dedicated to investigating the regulatory effects of the lncRNA nuclear paraspeckle assembly transcript 1 (Neat1) on liver fibrosis and HSC activation. Upregulation of Neat1 and cytohesin 3 (Cyth3) and downregulation of miR-148a-3p and miR-22-3p were observed in mouse fibrotic liver tissues. Knockdown of Neat1 or Cyth3 attenuated liver fibrosis and collagen deposition in vivo and the activation of HSCs in vitro. An miR-148a-3p and miR-22-3p inhibitor facilitated HSC activation and collagen fiber expression. Neat1 directly targeted miR-148a-3p and miR-22-3p to modulate Cyth3 expression. Knockdown of Neat1 inhibited Cyth3 expression via the competing endogenous RNA (ceRNA) mechanism of sponging miR-148a-3p and miR-22-3p to regulate liver fibrosis and HSC activation. The ceRNA regulatory network may promote a better understanding of liver fibrogenesis, contribute to an original agreement of liver fibrosis etiopathogenesis and provide insights into the development of a novel domain of lncRNA-directed therapy against liver fibrosis.