Deficiency of 15-LOX-1 induces radioresistance through downregulation of MacroH2A2 in colorectal cancer

Yoo Jin Na, Bo Ram Kim, Jung Lim Kim, Sanghee Kang, Yoon A. Jeong, Seong Hye Park, Min Jee Jo, Jeong Yub Kim, Hong Jun Kim, Sang Cheul Oh, Dae Hee Lee

Research output: Contribution to journalArticle

Abstract

Despite the importance of radiation therapy, there are few radiation-related markers available for use in clinical practice. A larger catalog of such biomarkers is required to help clinicians decide when radiotherapy should be replaced with a patient-specific treatment. Arachidonate 15-lipoxygenase (15-LOX-1) enzyme is involved in polyunsaturated fatty acid metabolism. When colorectal cancer (CRC) cells were exposed to radiation, 15-LOX-1 was upregulated. To verify whether 15-LOX-1 protects against or induces DNA damage, we irradiated sh15-LOX-1 stable cells. We found that low 15-LOX-1 is correlated with radioresistance in CRC cells. These data suggest that the presence of 15-LOX-1 can be used as a marker for radiation-induced DNA damage. Consistent with this observation, gene-set-enrichment analysis based on microarray experiments showed that UV_RESPONSE was decreased in sh15-LOX-1 cells compared to shCon cells. Moreover, we discovered that the expression of the histone H2A variant macroH2A2 was sevenfold lower in sh15-LOX-1 cells. Overall, our findings present mechanistic evidence that macroH2A2 is transcriptionally regulated by 15-LOX-1 and suppresses the DNA damage response in irradiated cells by delaying H2AX activation.

Original languageEnglish
Article number1776
JournalCancers
Volume11
Issue number11
DOIs
Publication statusPublished - 2019 Nov

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Keywords

  • 15-LOX-1
  • Colorectal cancer
  • DNA damage
  • MacroH2A2
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Na, Y. J., Kim, B. R., Kim, J. L., Kang, S., Jeong, Y. A., Park, S. H., Jo, M. J., Kim, J. Y., Kim, H. J., Oh, S. C., & Lee, D. H. (2019). Deficiency of 15-LOX-1 induces radioresistance through downregulation of MacroH2A2 in colorectal cancer. Cancers, 11(11), [1776]. https://doi.org/10.3390/cancers11111776