Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Canceropen access
- Authors
- Na, Yoo Jin; Kim, Bo Ram; Kim, Jung Lim; Kang, Sanghee; Jeong, Yoon A.; Park, Seong Hye; Jo, Min Jee; Kim, Jeong-Yub; Kim, Hong Jun; Oh, Sang Cheul; Lee, Dae Hee
- Issue Date
- Nov-2019
- Publisher
- MDPI
- Keywords
- 15-LOX-1; colorectal cancer; radiation; macroH2A2; DNA damage
- Citation
- CANCERS, v.11, no.11
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCERS
- Volume
- 11
- Number
- 11
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1496
- DOI
- 10.3390/cancers11111776
- ISSN
- 2072-6694
2072-6694
- 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.
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- Appears in
Collections - 3. Graduate School > Graduate School > 1. Journal Articles
- 4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles
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