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CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas

Summary Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of gli...

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Published in:CNS neuroscience & therapeutics 2016-06, Vol.22 (6), p.518-524
Main Authors: Liu, Da‐Ming, Wang, Hong‐Jun, Han, Bo, Meng, Xiang‐Qi, Chen, Ming‐Hui, Yang, Dong‐Bo, Sun, Ying, Li, Yong‐Li, Jiang, Chuan‐Lu
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cited_by cdi_FETCH-LOGICAL-c4761-850a8ec836097fe130212d3bc34924eec784e6f45ce5449e1f2c8c8e10ae14023
cites cdi_FETCH-LOGICAL-c4761-850a8ec836097fe130212d3bc34924eec784e6f45ce5449e1f2c8c8e10ae14023
container_end_page 524
container_issue 6
container_start_page 518
container_title CNS neuroscience & therapeutics
container_volume 22
creator Liu, Da‐Ming
Wang, Hong‐Jun
Han, Bo
Meng, Xiang‐Qi
Chen, Ming‐Hui
Yang, Dong‐Bo
Sun, Ying
Li, Yong‐Li
Jiang, Chuan‐Lu
description Summary Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high‐grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.
doi_str_mv 10.1111/cns.12531
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Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high‐grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.</description><identifier>ISSN: 1755-5930</identifier><identifier>EISSN: 1755-5949</identifier><identifier>DOI: 10.1111/cns.12531</identifier><identifier>PMID: 27012733</identifier><language>eng</language><publisher>England: John Wiley &amp; Sons, Inc</publisher><subject>Brain Neoplasms - diagnosis ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics ; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism ; CAMKK2 ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; DNA Methylation - genetics ; Female ; Gene Expression Regulation, Neoplastic - genetics ; Genes ; Glioma ; Glioma - diagnosis ; Glioma - genetics ; Glioma - mortality ; Glioma - pathology ; Humans ; Male ; Microarray Analysis ; Original ; Prognosis ; Progression ; Promoter Regions, Genetic ; Survival Analysis</subject><ispartof>CNS neuroscience &amp; therapeutics, 2016-06, Vol.22 (6), p.518-524</ispartof><rights>2016 John Wiley &amp; Sons Ltd</rights><rights>2016 John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2016 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4761-850a8ec836097fe130212d3bc34924eec784e6f45ce5449e1f2c8c8e10ae14023</citedby><cites>FETCH-LOGICAL-c4761-850a8ec836097fe130212d3bc34924eec784e6f45ce5449e1f2c8c8e10ae14023</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/PMC6492904/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492904/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,11561,27923,27924,46051,46475,53790,53792</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fcns.12531$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27012733$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Da‐Ming</creatorcontrib><creatorcontrib>Wang, Hong‐Jun</creatorcontrib><creatorcontrib>Han, Bo</creatorcontrib><creatorcontrib>Meng, Xiang‐Qi</creatorcontrib><creatorcontrib>Chen, Ming‐Hui</creatorcontrib><creatorcontrib>Yang, Dong‐Bo</creatorcontrib><creatorcontrib>Sun, Ying</creatorcontrib><creatorcontrib>Li, Yong‐Li</creatorcontrib><creatorcontrib>Jiang, Chuan‐Lu</creatorcontrib><title>CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas</title><title>CNS neuroscience &amp; therapeutics</title><addtitle>CNS Neurosci Ther</addtitle><description>Summary Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high‐grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.</description><subject>Brain Neoplasms - diagnosis</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - pathology</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism</subject><subject>CAMKK2</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>DNA Methylation - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes</subject><subject>Glioma</subject><subject>Glioma - diagnosis</subject><subject>Glioma - genetics</subject><subject>Glioma - mortality</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Microarray Analysis</subject><subject>Original</subject><subject>Prognosis</subject><subject>Progression</subject><subject>Promoter Regions, Genetic</subject><subject>Survival Analysis</subject><issn>1755-5930</issn><issn>1755-5949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkV1PFDEUhhuikQ-98A-YJt5IwkI_p-2NCVk-JLBqBK6bbvfMUpyZQjsD2X9v14UNmpjYmzY9T55z2heh95Ts07IOfJf3KZOcbqAtqqQcSSPMq_WZk020nfMtIRXTRr9Bm0wRyhTnW-hqfDg5P2d7-AfMh8b1MMPTBf6eYht7SHgC_c2iXIfY7eGQsVuW5l3MffB44tLPwoQOH4W6HjLg0ybE1uW36HXtmgzvnvYddH1yfDX-Mrr4dno2PrwYeaEqOtKSOA1e84oYVQPlhFE241PPhWECwCstoKqF9CCFMEBr5rXXQIkDKgjjO-jzyns3TFuYeej65Bp7l0Lr0sJGF-yflS7c2Hl8sFVpYIgogk9PghTvB8i9bUP20DSugzhkS5UhRjAh1H-g2hDOJTEF_fgXehuH1JWfWFK6UqaSy-F3V5RPMecE9XpuSuwyVltitb9jLeyHlw9dk885FuBgBTyGBhb_Ntnx18uV8hcL3apG</recordid><startdate>201606</startdate><enddate>201606</enddate><creator>Liu, Da‐Ming</creator><creator>Wang, Hong‐Jun</creator><creator>Han, Bo</creator><creator>Meng, Xiang‐Qi</creator><creator>Chen, Ming‐Hui</creator><creator>Yang, Dong‐Bo</creator><creator>Sun, Ying</creator><creator>Li, Yong‐Li</creator><creator>Jiang, Chuan‐Lu</creator><general>John Wiley &amp; 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Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>CNS neuroscience &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Liu, Da‐Ming</au><au>Wang, Hong‐Jun</au><au>Han, Bo</au><au>Meng, Xiang‐Qi</au><au>Chen, Ming‐Hui</au><au>Yang, Dong‐Bo</au><au>Sun, Ying</au><au>Li, Yong‐Li</au><au>Jiang, Chuan‐Lu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas</atitle><jtitle>CNS neuroscience &amp; therapeutics</jtitle><addtitle>CNS Neurosci Ther</addtitle><date>2016-06</date><risdate>2016</risdate><volume>22</volume><issue>6</issue><spage>518</spage><epage>524</epage><pages>518-524</pages><issn>1755-5930</issn><eissn>1755-5949</eissn><abstract>Summary Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high‐grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.</abstract><cop>England</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>27012733</pmid><doi>10.1111/cns.12531</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Brain Neoplasms - diagnosis
Brain Neoplasms - genetics
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics
Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism
CAMKK2
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
DNA Methylation - genetics
Female
Gene Expression Regulation, Neoplastic - genetics
Genes
Glioma
Glioma - diagnosis
Glioma - genetics
Glioma - mortality
Glioma - pathology
Humans
Male
Microarray Analysis
Original
Prognosis
Progression
Promoter Regions, Genetic
Survival Analysis
title CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas
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