Histone acetyltransferase 1 up regulates Bcl2L12 expression in nasopharyngeal cancer cells

Arch Biochem Biophys. 2018 May 15:646:72-79. doi: 10.1016/j.abb.2018.03.040. Epub 2018 Apr 3.

Abstract

The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry. The results showed that by screening the subtypes of HAT, the levels of HAT1 were uniquely higher in NPC as compared with non-cancer nasopharyngeal tissue. The levels of Bcl2L12 in NPC cells were positively correlated with HAT1. HAT1 involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment.

Keywords: Apoptosis; Bcl2L12; HAT1; Histone acetyltransferase; Nasopharyngeal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Liposomes / metabolism
  • Male
  • Middle Aged
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Plasmids
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering / genetics
  • STAT5 Transcription Factor / metabolism
  • Up-Regulation

Substances

  • BCL2L12 protein, human
  • Liposomes
  • Muscle Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • STAT5 Transcription Factor
  • Histone Acetyltransferases
  • histone acetyltransferase type B complex