LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition

Commun Biol. 2023 Mar 18;6(1):285. doi: 10.1038/s42003-023-04670-z.

Abstract

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Collagen / metabolism
  • Epithelial-Mesenchymal Transition*
  • Hepatic Stellate Cells* / metabolism
  • Hippo Signaling Pathway*
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • Collagen
  • MicroRNAs
  • MIRN-3085 microRNA, human
  • RNA, Long Noncoding
  • Miat long non-coding RNA