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

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Tumor Biology

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Xueli Pang

  2. Department of Medical Genetics, College of Basic Medicine, Third Military Medical University, Chongqing, 400038, China

    Gang He, Chao Luo, Yan Wang & Bo Zhang

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  1. Xueli Pang
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  2. Gang He
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  3. Chao Luo
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  4. Yan Wang
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Correspondence to Bo Zhang.

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Pang, X., He, G., Luo, C. et al. Knockdown of Rad9A enhanced DNA damage induced by trichostatin A in esophageal cancer cells. Tumor Biol. 37, 963–970 (2016). https://doi.org/10.1007/s13277-015-3879-z

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  • DOI: https://doi.org/10.1007/s13277-015-3879-z

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