LncRNA GHET1 activated by H3K27 acetylation promotes cell tumorigenesis through regulating ATF1 in hepatocellular carcinoma

Biomed Pharmacother. 2017 Oct:94:326-331. doi: 10.1016/j.biopha.2017.07.046. Epub 2017 Jul 31.

Abstract

Background: GHET1 is one of tumor-related lncRNAs. We aimed to explore the functional involvement of GHET1 in hepatocellular carcinoma (HCC).

Methods: In this study, HCC tissues and the paired normal tissues were collected for the detection of target molecules. The expression level of target molecules in HCC tissues or cell lines was determined by qRT-PCR and western blot, respectively. The expression of endogenous GHET1 and ATF1 was modulated by using cell transfection. RNA pull down assay was performed to examine the interaction between GHET1 and ATF1. ChIP assay was conducted to determine the H3K27Ac acetylation of GHET1 promoter.

Results: H3K27 acetylation activated-GHET1 was upregulated in HCC tissues and cell lines. Moreover, GHET1 silencing could inhibit the proliferation, migration, invasion and EMT of HCC cells in vitro. GHET1 could regulate the expression of ATF1 mRNA and protein; RNA pull-down assays supported that GHET1 could bind to ATF1 protein. Furthermore, overexpression of ATF1 almost completely reversed the GHET1 knockdown mediated inhibition on the proliferation, migration, invasion and EMT of HCC cells.

Conclusion: LncRNA GHET1 was intimately involved in the occurrence and development of HCC through regulating ATF1.

Keywords: ATF1; GHET1; H3K27 acetylation; Hepatocellular carcinoma (HCC).

MeSH terms

  • Acetylation
  • Activating Transcription Factor 1 / genetics
  • Activating Transcription Factor 1 / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Knockdown Techniques
  • Histones / metabolism*
  • Humans
  • Liver Neoplasms / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transfection
  • Up-Regulation

Substances

  • ATF1 protein, human
  • Activating Transcription Factor 1
  • GHET1 transcript, human
  • Histones
  • RNA, Long Noncoding