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Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896202/
https://www.ncbi.nlm.nih.gov/pubmed/31717983
http://dx.doi.org/10.3390/cancers11111776
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author 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
author_facet 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
author_sort Na, Yoo Jin
collection PubMed
description 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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spelling pubmed-68962022019-12-23 Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer 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 Cancers (Basel) Article 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. MDPI 2019-11-11 /pmc/articles/PMC6896202/ /pubmed/31717983 http://dx.doi.org/10.3390/cancers11111776 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title_full Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title_fullStr Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title_full_unstemmed Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title_short Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer
title_sort deficiency of 15-lox-1 induces radioresistance through downregulation of macroh2a2 in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896202/
https://www.ncbi.nlm.nih.gov/pubmed/31717983
http://dx.doi.org/10.3390/cancers11111776
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