LncRNA WWOX-AS1 sponges miR-20b-5p in hepatocellular carcinoma and represses its progression by upregulating WWOX

Cancer Biol Ther. 2020 Oct 2;21(10):927-936. doi: 10.1080/15384047.2020.1806689. Epub 2020 Sep 15.

Abstract

Increasing evidence has revealed that long noncoding RNAs (lncRNAs) emerge as pivotal regulators in diverse cancers, including hepatocellular carcinoma (HCC). This study was conducted to investigate the role of lncRNA WWOX antisense RNA 1 (WWOX-AS1) in HCC progression. Our present study illustrated that WWOX-AS1 was lowly expressed in HCC tissues and cell lines. High WWOX-AS1 expression was further confirmed to predict a favorable prognosis in HCC patients. Through functional assays, we observed that upregulated WWOX-AS1 was correlated with decreased cell proliferation, migration, epithelial to mesenchymal transition (EMT) process and increased cell apoptosis, suggesting that WWOX-AS1 exerted anti-carcinogenic role in the development of HCC. Moreover, WWOX, the nearby gene of WWOX-AS1, was found at a low level in HCC tissues and cell lines. Furthermore, there was a positive relationship between WWOX-AS1 and WWOX. Additionally, WWOX overexpression hampered cell proliferation, migration, EMT process and induced cell apoptosis in HCC. Mechanically, WWOX-AS1 was identified as a cytoplasmic RNA in HCC cells and sponged miR-20b-5p to regulate WWOX expression. Rescue assays further indicated that WWOX knockdown counteracted WWOX-AS1 overexpression-mediated suppressive function on HCC progression. Collectively, WWOX-AS1/miR-20b-5p/WWOX axis suppresses HCC tumorigenesis, hinting a potential molecular mechanism for the therapy of HCC patients.

Keywords: HCC; WWOX; WWOX-AS1; miR-20b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation
  • WW Domain-Containing Oxidoreductase / genetics
  • WW Domain-Containing Oxidoreductase / metabolism*

Substances

  • MIRN20b microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • Tumor Suppressor Proteins
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human

Grants and funding

This study was supported by Hainan Natural Science Foundation (No. 20158274).