Radiation-induced cxcl12 upregulation via histone modification at the promoter in the tumor microenvironment of hepatocellular carcinoma

Hak Jun Ahn, Soon Young Hwang, Ngoc Hoan Nguyen, Ik Jae Lee, Eun Jeong Lee, Jinsil Seong, Jong Soo Lee

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11 Citations (Scopus)


Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24 cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

Original languageEnglish
Pages (from-to)530-545
Number of pages16
JournalMolecules and cells
Issue number7
Publication statusPublished - 2019

Bibliographical note

Funding Information:
We thank all members of Lee’s laboratory for their helpful advice. This work was supported by the grants from the National Research Foundation of Korea (NRF) (2017M2A2A7A01021034 and 2017R1A2B4010146).

Publisher Copyright:
© The Korean Society for Molecular and Cellular Biology. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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