EP300 regulates the expression of human survivin gene in esophageal squamous cell carcinoma

نویسندگان

  • Xiaoya Yang
  • Zhu Li
  • Yintu Ma
  • Xuhua Yang
  • Jun Gao
  • Surui Liu
  • Gengyin Wang
چکیده

Survivin is selectively up-regulated in various cancers including esophageal squamous cell carcinoma (ESCC). The underlying mechanism of survivin overexpression in cancers is needed to be further studied. In this study, we investigated the effect of EP300, a well known transcriptional coactivator, on survivin gene expression in human esophageal squamous cancer cell lines. We found that overexpression of EP300 was associated with strong repression of survivin expression at the mRNA and protein levels. Knockdown of EP300 increased the survivin expression as indicated by western blotting and RT-PCR analysis. Furthermore, our results indicated that transcriptional repression mediated by EP300 regulates survivin expression levels via regulating the survivin promoter activity. Chromatin immunoprecipitation (ChIP) analysis revealed that EP300 was associated with survivin gene promoter. When EP300 was added to esophageal squamous cancer cells, increased EP300 association was observed at the survivin promoter. But the acetylation level of histone H3 at survivin promoter didn’t change after RNAi-depletion of endogenous EP300 or after overexpression of EP300. These findings establish a negative regulatory role for EP300 in survivin expression.

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تاریخ انتشار 2016