miR-296-5p suppresses stem cell potency of hepatocellular carcinoma cells via regulating Brg1/Sall4 axis

Cell Signal. 2020 Aug:72:109650. doi: 10.1016/j.cellsig.2020.109650. Epub 2020 Apr 19.

Abstract

Epithelial-mesenchymal transition (EMT), a pivotal event during cancer progression such as relapse and metastasis, is positively correlated with the stemness potency of tumor cells. Our previous study showed that miR-296-5p attenuated EMT program of hepatocellular carcinoma cells (HCC) through NRG1/ERBB2/ERBB3 signaling. In the present study, we uncovered that miR-296-5p was able to inhibit the stemness potency of HCC by decreasing the number and size of tumorspheres, downregulating the expression of CSC biomarkers and hampering the ability of tumorigenesis in NOD/SCID mice. Brahma-related gene-1 (Brg1), as the target protein of miR-296-5p detected by bioinformatics methods, activates a series of downstream cascades through directly binding to Sall4 promoter and enhancing Sall4 transcription. Importantly, the higher expressions of Brg1 and Sall4 in tumor tissues of HCC patients suggest poorer prognoses after surgical extraction. In conclusion, miR-296-5p exerts an inhibitory effect on stemness potency of HCC cells via Brg1/Sall4 axis.

Keywords: HCC; Stemness; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • DNA Helicases / metabolism*
  • Down-Regulation / genetics
  • Epithelial Cell Adhesion Molecule / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Thy-1 Antigens / metabolism
  • Transcription Factors / metabolism*

Substances

  • Epithelial Cell Adhesion Molecule
  • MIRN296 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • SALL4 protein, human
  • Thy-1 Antigens
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases