hMOF (human males absent on the first), an oncogenic protein of human oral tongue squamous cell carcinoma, targeting EZH2 (enhancer of zeste homolog 2)

Cell Prolif. 2015 Aug;48(4):436-42. doi: 10.1111/cpr.12177. Epub 2015 Jun 1.

Abstract

Objectives: MOF (males absent on the first) is a histone acetyltransferase belonging to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. In mammals, MOF plays critical roles in transcription activation by acetylating histone H4 at K16. Human MOF (hMOF) essentially participates in behaviour of several human cancers. However, its role in human oral tongue squamous cell carcinoma (OTSCC) remains elusive, but we propose that hMOF regulates OTSCC cell population growth.

Materials and methods: Real time PCR and western blot analysis were applied, and it was found that hMOF level was up-regulated in human OTSCC. High hMOF expression predicted poor overall and disease-free survival. hMOF knockdown attenuated OTSCC cell growth and transformation.

Results: EZH2 (enhancer of zeste homolog 2) was up-regulated in human OTSCC tissues and its level positively correlated with level of hMOF. hMOF knockdown inhibited EZH2 expression by reducing its promoter activity. Moreover, we have demonstrated that EZH2 was critically essential for function of hMOF in human OTSCC.

Conclusions: Human males absent on the first regulated OSTCC growth through EZH2, thus EZH2 may serve as a candidate for anti-OTSCC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Histone Acetyltransferases / genetics*
  • Humans
  • Mice, Inbred BALB C
  • Polycomb Repressive Complex 2 / genetics*
  • Tongue / metabolism
  • Tongue / pathology
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology

Substances

  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Histone Acetyltransferases
  • KAT8 protein, human