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지방산 분해효소(ALOX15; 15-LOX-1) 발현 여하에 따른 방사선 감수성 차이는 지방산 분해 효소에 의해 조절되는 히스톤(H2AFY2; MacroH2A2)에 의한 방사선 반응성 조절에 기인한다.     

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.

Author information

Na YJ1, Kim BR2, Kim JL2, Kang S3, Jeong YA1, Park SH1, Jo MJ1, Kim JY4, Kim HJ5, Oh SC2, Lee DH2,6.
1
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea.
2
Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea.
3
Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea.
4
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
5
Division of Oncology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul 02447, Korea.
6
Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneung, Gangwon 210-702, Korea.

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