HDAC5, negatively regulated by miR-148a-3p, promotes colon cancer cell migration

Cancer Sci. 2022 Aug;113(8):2560-2574. doi: 10.1111/cas.15399. Epub 2022 Jun 5.

Abstract

Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR-148a-3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR-148a-3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR-148a-3p.

Keywords: HDAC5; colon adenocarcinoma; invasion; miR-148a-3p; migration.

MeSH terms

  • Adenocarcinoma* / genetics
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms* / genetics
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylases* / genetics
  • Histone Deacetylases* / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics

Substances

  • MIRN148 microRNA, human
  • MicroRNAs
  • HDAC5 protein, human
  • Histone Deacetylases