LncRNA MAGI2-AS3 inhibits hepatocellular carcinoma cell proliferation and migration by targeting the miR-374b-5p/SMG1 signaling pathway

J Cell Physiol. 2019 Aug;234(10):18825-18836. doi: 10.1002/jcp.28521. Epub 2019 Mar 28.

Abstract

Long noncoding RNAs (lncRNAs) have been proven to play critical roles in cancer progression. Recently, lncRNA MAGI2-AS3 has been revealed to be a tumor suppressor and inhibit cell growth by targeting the Fas/FasL signalling pathway in breast cancer. However, the role and underlying mechanism of MAGI2-AS3 in hepatocellular carcinoma (HCC) remain largely unknown. In the current study, we found that MAGI2-AS3 expression is downregulated in HCC tissues and closely associated with some clinical characteristics (tumor size, lymph node metastasis, and TNM stage) and poor overall survival. Overexpression of MAGI2-AS3 inhibits HCC cell proliferation and migration in vitro, while impedes tumor growth in vivo accordantly. In addition, our data suggest that MAGI2-AS3 could function as an endogenous sponge of miR-374b-5p by directly binding to it and suppressing its expression. Furthermore, miR-374b-5p upregulation could restore the inhibitory effect of MAGI2-AS3 on HCC cells processes. Moreover, suppressor with morphogenetic effect on genitalia family member 1 (SMG1) is positively regulated by MAGI2-AS3 via absorbing miR-374b-5p in HCC cells. More important, SMG1 knockdown reverses the suppressive function of MAGI2-AS3 in HCC cell processes. Taken together, we reveal a functional MAGI2-AS3/miR-374b-5p/SMG1 axis that suppresses HCC progression, potently suggesting a new road for HCC treatment.

Keywords: HCC progression; MAGI2-AS3; SMG1; miR-374b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multivariate Analysis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction*
  • Treatment Outcome
  • Up-Regulation

Substances

  • MIRN374 microRNA 374, human
  • MicroRNAs
  • RNA, Long Noncoding