Tumor Biology

, Volume 37, Issue 1, pp 963–970 | Cite as

Knockdown of Rad9A enhanced DNA damage induced by trichostatin A in esophageal cancer cells

Original Article

Abstract

Histone deacetylase (HDAC) inhibitors have recently emerged as a new class of anticancer agents. As a classical HDAC inhibitor, trichostatin A (TSA) has been shown to possess many anticancer activities such as induction of cell cycle arrest, promotion of cell death, and enhancement of radiosensitity. In our previous work, we found that TSA treatment induced Rad9 gene expression, which suggested that Rad9 might play a role in TSA-induced biological effects. As Rad9 is involved in maintaining genomic integrity, we further analyzed the DNA damage induced by TSA and combined with Rad9 knockdown in esophageal cancer cells (ESCCs). Our results showed that TSA treatment alone induced significantly DNA damage in ESCC cells. Simultaneously, TSA also induced Rad9 gene expression both at transcriptional and translational levels in EC109 cells, but not in KYSE150 cells. Further, the induction of Rad9 by TSA was accompanied with increased level of histone H3K9 acetylation in Rad9 promoter region. To understand the role of Rad9 in TSA-induced DNA damage, Rad9 gene expression was efficiently knocked down by small interfering RNA (siRNA), which led to enhanced DNA damage and cell death induced by TSA. Our data suggested that Rad9 plays an important role in DNA damage, which is related to the biological effects of TSA.

Keywords

TSA Esophageal cancer DNA damage Rad9A Apoptosis 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81272497).

Conflicts of interest

None

Supplementary material

13277_2015_3879_MOESM1_ESM.docx (165 kb)
ESM 1 (DOCX 165 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xueli Pang
    • 1
  • Gang He
    • 2
  • Chao Luo
    • 2
  • Yan Wang
    • 2
  • Bo Zhang
    • 2
  1. 1.Department of Oncology, Southwest HospitalThird Military Medical UniversityChongqingChina
  2. 2.Department of Medical Genetics, College of Basic MedicineThird Military Medical UniversityChongqingChina

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