HDAC2 promotes the EMT of colorectal cancer cells and via the modular scaffold function of ENSG00000274093.1

J Cell Mol Med. 2021 Jan;25(2):1190-1197. doi: 10.1111/jcmm.16186. Epub 2020 Dec 15.

Abstract

Histone deacetylase 2 (HDAC2), a member of the Histone deacetylase family, plays a vital role in various carcinomas. In this study, we identified that HDAC2 expression levels are associated with liver metastasis, higher T stages and poor prognosis in colorectal cancer. HDAC2 down-regulation via lentivirus-mediated expression of HDAC2-targeting shRNA reduced the in vitro migration and invasion ability of HCT116 cell as well as their liver metastasis in nude mouse xenografts. Mechanistically, HDAC2 promotes epithelial-mesenchymal transition (EMT) in colorectal cancer cells by combining HDAC1 with EZH2 (a key histone methyltransferase), possibly through the modular scaffold function of a new lncRNA, ENSG00000274093.1. HDAC2 thus appears to promote CRC cell migration and invasion through binding HDAC1 and EZH2 via ENSG00000274093.1.

Keywords: colorectal cancer; epithelial-mesenchymal transition; histone deacetylase 2; long non-coding RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Histone Deacetylase 1 / metabolism
  • Histone Deacetylase 2 / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • RNA, Long Noncoding
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2