4.6 Article

SAHA inhibits the transcription initiation of HPV18 E6/E7 genes in HeLa cervical cancer cells

Journal

GENE
Volume 553, Issue 2, Pages 98-104

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2014.10.007

Keywords

Human papillomavirus; E6 and E7; Transcription; SAHA; Histone acetylation; Cervical cancer

Funding

  1. National Natural Science Foundation of China [31301073]
  2. Applied Basic Science and Frontier Technology Program of Tianjin [13JCYBJC38000]
  3. Zhejiang University through the National 985 Platform
  4. China National 973 project [2014CB542003]
  5. China Natural Sciences Foundation project [81372179]
  6. Zhejiang Provincial Natural Sciences Foundation project [LY13C070001]
  7. Fundamental Research Funds for the Central Universities, National Ministry of Education, China

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High risk human papillomavirus (HPV) is a well recognized causative agent of cervical cancer. Suberoylanilide hydroxamic acid (SAHA) is a potential anti-cervical cancer drug; however, its effect on the expression of HPV E6 and E7 genes remains unclear. Here, we show that, in SAHA treated HeLa cells, HPV18 E6 and E7 mRNA and protein levels were reduced, HPV18 promoter activity was decreased, and the association of RNP II with HPV18 promoter was diminished, suggesting that SAHA inhibited the transcription initiation of HPV18 E6 and E7 genes. In SARA-treated HeLa, although the level of lysine 9-acetylated histone H3 in the whole cell extracts increased obviously, its enrichment on HPV18 promoter was significantly reduced which is correlated with the down-regulation of HPV E6 and E7. (C) 2014 Published by Elsevier B.V.

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