아주대 / 안학준, 이종수*
Abstract
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.
Author information
Ahn HJ1,2, Hwang SY1,3,2, Nguyen NH1, Lee IJ4, Lee EJ4, Seong J4, Lee JS1,3.
1
Department of Life Science, College of Natural Sciences.
2
These authors contributed equally to this work.
3
Functional Cellunomics Institute, Ajou University, Suwon 16499, Korea.
4
Department of Radiation Oncology, Yonsei University Medical College, Yonsei University Health System, Seoul 03722, Korea.
편집위원
CXCL12 유전자의 후성유전학적 변화 원인을 다양하게 연구중이지만, 방사선에 의해 조절되는 직접적인 원인을 간암세포 모델에서, 후성유전학적 분자기전을 통해 분석한 연구결과라서 흥미로움.
2019-08-30 10:06:30