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Cited 3 time in webofscience Cited 2 time in scopus
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Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Canceropen access

Authors
Na, Yoo JinKim, Bo RamKim, Jung LimKang, SangheeJeong, Yoon A.Park, Seong HyeJo, Min JeeKim, Jeong-YubKim, Hong JunOh, Sang CheulLee, 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
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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3. Graduate School > Graduate School > 1. Journal Articles
2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles
4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles

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Oh, Sang Cheul
Guro Hospital (Department of Medical Oncology and Hematology, Guro Hospital)
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