Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss
Abstract Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop...
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Veröffentlicht in: | Journal of radiation research 2022-05, Vol.63 (3), p.331-341 |
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Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC. |
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Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC.</description><identifier>ISSN: 0449-3060</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1093/jrr/rrac004</identifier><identifier>PMID: 35333349</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Biotechnology industry ; Cancer ; Cell Line, Tumor ; Cell Proliferation ; Chemotherapy ; Class III Phosphatidylinositol 3-Kinases - metabolism ; Class III Phosphatidylinositol 3-Kinases - pharmacology ; Esophageal cancer ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - radiotherapy ; Esophageal Squamous Cell Carcinoma - genetics ; Esophageal Squamous Cell Carcinoma - radiotherapy ; Fundamental Radiation Science ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases - genetics ; Jumonji Domain-Containing Histone Demethylases - metabolism ; Jumonji Domain-Containing Histone Demethylases - pharmacology ; Mediation ; Methylation ; Nuclear Proteins - metabolism ; Photographic industry ; Promoter Regions, Genetic - genetics ; Radiotherapy ; Repressor Proteins - metabolism ; Repressor Proteins - pharmacology ; Squamous cell carcinoma</subject><ispartof>Journal of radiation research, 2022-05, Vol.63 (3), p.331-341</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-5eb3bbbc20f2a1fccb71efb7b404b385a7a7651805dedf270914c5b94df96c173</citedby><cites>FETCH-LOGICAL-c569t-5eb3bbbc20f2a1fccb71efb7b404b385a7a7651805dedf270914c5b94df96c173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124615/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124615/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35333349$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Gu, Min</creatorcontrib><creatorcontrib>Ju, Yongjian</creatorcontrib><creatorcontrib>Zhou, Juying</creatorcontrib><title>Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss</title><title>Journal of radiation research</title><addtitle>J Radiat Res</addtitle><description>Abstract
Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC.</description><subject>Biotechnology industry</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Chemotherapy</subject><subject>Class III Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Class III Phosphatidylinositol 3-Kinases - pharmacology</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - radiotherapy</subject><subject>Esophageal Squamous Cell Carcinoma - genetics</subject><subject>Esophageal Squamous Cell Carcinoma - radiotherapy</subject><subject>Fundamental Radiation Science</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Jumonji Domain-Containing Histone Demethylases - genetics</subject><subject>Jumonji Domain-Containing Histone Demethylases - metabolism</subject><subject>Jumonji Domain-Containing Histone Demethylases - pharmacology</subject><subject>Mediation</subject><subject>Methylation</subject><subject>Nuclear Proteins - metabolism</subject><subject>Photographic industry</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Radiotherapy</subject><subject>Repressor Proteins - metabolism</subject><subject>Repressor Proteins - pharmacology</subject><subject>Squamous cell carcinoma</subject><issn>0449-3060</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kt9rFDEQxxdR7Fl98l0CggiybbJJNpcXoZ6_Siv1QZ9Dkp3spexutsnuwf0F_ttmubNYEJOHDJnPfJkZvkXxkuAzgiU9v43xPEZtMWaPihWhTJaScPG4WGGWY4prfFI8S-kW40pgjp8WJ5TTfJhcFb9udhBt6P3QoqgbH8oIyadJDxaQHxCkMG51C7pD6W7WfZgTstB1yOpo_RB6jXZeo-1-hNjDtN13evJhQMGh75dXdEPRGEMfJogoQrtkemi8nqBBZo-uPn7jH1AXUnpePHG6S_Di-J4WPz9_-rH5Wl7ffLncXFyXltdyKjkYaoyxFXaVJs5aIwg4IwzDzNA110KLmpM15g00Lo8rCbPcSNY4WVsi6Gnx_qA7ziZ3YmGYou7UGH2v414F7dXDzOC3qg07JUnFasKzwNujQAx3M6RJ9T4tG9ED5OWoqmYMY0HXOKOvD2irO1B-cCEr2gVXF6KWWNRELB2d_YPKt4He2zCA8_n_QcG7Q4GNeXER3H33BKvFESo7Qh0dkelXfw98z_6xQAbeHIAwj_9V-g3WB8Jf</recordid><startdate>20220518</startdate><enddate>20220518</enddate><creator>Wang, Xiaobo</creator><creator>Gu, Min</creator><creator>Ju, Yongjian</creator><creator>Zhou, Juying</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220518</creationdate><title>Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss</title><author>Wang, Xiaobo ; Gu, Min ; Ju, Yongjian ; Zhou, Juying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-5eb3bbbc20f2a1fccb71efb7b404b385a7a7651805dedf270914c5b94df96c173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biotechnology industry</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Chemotherapy</topic><topic>Class III Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Class III Phosphatidylinositol 3-Kinases - pharmacology</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - radiotherapy</topic><topic>Esophageal Squamous Cell Carcinoma - genetics</topic><topic>Esophageal Squamous Cell Carcinoma - radiotherapy</topic><topic>Fundamental Radiation Science</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Jumonji Domain-Containing Histone Demethylases - genetics</topic><topic>Jumonji Domain-Containing Histone Demethylases - metabolism</topic><topic>Jumonji Domain-Containing Histone Demethylases - pharmacology</topic><topic>Mediation</topic><topic>Methylation</topic><topic>Nuclear Proteins - metabolism</topic><topic>Photographic industry</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Radiotherapy</topic><topic>Repressor Proteins - metabolism</topic><topic>Repressor Proteins - pharmacology</topic><topic>Squamous cell carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Gu, Min</creatorcontrib><creatorcontrib>Ju, Yongjian</creatorcontrib><creatorcontrib>Zhou, Juying</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiaobo</au><au>Gu, Min</au><au>Ju, Yongjian</au><au>Zhou, Juying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss</atitle><jtitle>Journal of radiation research</jtitle><addtitle>J Radiat Res</addtitle><date>2022-05-18</date><risdate>2022</risdate><volume>63</volume><issue>3</issue><spage>331</spage><epage>341</epage><pages>331-341</pages><issn>0449-3060</issn><eissn>1349-9157</eissn><abstract>Abstract
Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35333349</pmid><doi>10.1093/jrr/rrac004</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biotechnology industry Cancer Cell Line, Tumor Cell Proliferation Chemotherapy Class III Phosphatidylinositol 3-Kinases - metabolism Class III Phosphatidylinositol 3-Kinases - pharmacology Esophageal cancer Esophageal Neoplasms - genetics Esophageal Neoplasms - radiotherapy Esophageal Squamous Cell Carcinoma - genetics Esophageal Squamous Cell Carcinoma - radiotherapy Fundamental Radiation Science Gene Expression Regulation, Neoplastic Humans Jumonji Domain-Containing Histone Demethylases - genetics Jumonji Domain-Containing Histone Demethylases - metabolism Jumonji Domain-Containing Histone Demethylases - pharmacology Mediation Methylation Nuclear Proteins - metabolism Photographic industry Promoter Regions, Genetic - genetics Radiotherapy Repressor Proteins - metabolism Repressor Proteins - pharmacology Squamous cell carcinoma |
title | Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss |
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