Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway

J Cell Mol Med. 2019 Sep;23(9):6271-6282. doi: 10.1111/jcmm.14513. Epub 2019 Jul 2.

Abstract

Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non-coding RNA termed SNAI3-AS1 which was generally up-regulated in HCC tissues compared with normal control. Higher expression of SNAI3-AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3-AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3-AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3-AS1 could affect HCC tumorigenesis by binding up-frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF-β/Smad pathway. Functionally, SNAI3-AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3-AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF-β/Smad pathway.

Keywords: EMT; SNAI3-AS1; UPF1; hepatocellular carcinoma; metastasis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockout Techniques
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • RNA Helicases / genetics*
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Smad7 Protein / genetics*
  • Snail Family Transcription Factors / genetics
  • Trans-Activators / genetics*

Substances

  • RNA, Long Noncoding
  • SMAD7 protein, human
  • SNAI3 protein, human
  • Smad7 Protein
  • Snail Family Transcription Factors
  • Trans-Activators
  • RNA Helicases
  • UPF1 protein, human