Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1

  • Authors:
    • Myoung Jun Kim
    • Sung Kyung Choi
    • Seong Hwi Hong
    • Jung Woo Eun
    • Suk Woo Nam
    • Jeung-Whan Han
    • Jueng Soo You
  • View Affiliations

  • Published online on: May 2, 2018     https://doi.org/10.3892/ijo.2018.4392
  • Pages: 395-403
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Abstract

The interleukin-7 receptor (IL7R) is generally expressed in immune cells and is critical in survival, development and homeostasis in the immune system. Advanced genome-wide cancer studies have reported that IL7R is genetically amplified in human esophageal squamous cell carcinoma (ESCC), however, the exact role of IL7R in ESCC has not been investigated. In the present study, it was found that IL7R was overexpressed in ESCC cohorts and the loss of IL7R induced anti-oncogenic effects in ESCC cell lines. A small panel of epigenetic drugs were screened for their ability to downregulate the expression of IL7R. Unexpectedly, apicidin, a histone deacetylase (HDAC) inhibitor, effectively downregulated the expression of IL7R in a dose-dependent manner at an early time-point, as determined by quantitative polymerase chain reaction and IL7R immunostaining, and did not require de novo protein synthesis. Of note, apicidin induced the acetylation of Forkhead box-containing protein, O subfamily 1, which acts as a repressor at the IL7R promoter, accompanied with depleted active histone modifications based on chromatin immunoprecipitation assay. Taken together, these results demonstrated that targeting oncogenic IL7R in ESCC by HDAC inhibitors may be a valuable therapeutic approach.
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July 2018
Volume 53 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Kim, M., Choi, S., Hong, S., Eun, J., Nam, S., Han, J., & You, J. (2018). Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1. International Journal of Oncology, 53, 395-403. https://doi.org/10.3892/ijo.2018.4392
MLA
Kim, M., Choi, S., Hong, S., Eun, J., Nam, S., Han, J., You, J."Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1". International Journal of Oncology 53.1 (2018): 395-403.
Chicago
Kim, M., Choi, S., Hong, S., Eun, J., Nam, S., Han, J., You, J."Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1". International Journal of Oncology 53, no. 1 (2018): 395-403. https://doi.org/10.3892/ijo.2018.4392