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Role of STAT3 and vitamin D receptor in EZH2 ‐mediated invasion of human colorectal cancer

dc.contributor.authorLin, Yan‐weien_US
dc.contributor.authorRen, Lin‐linen_US
dc.contributor.authorXiong, Huaen_US
dc.contributor.authorDu, Wanen_US
dc.contributor.authorYu, Ya‐nanen_US
dc.contributor.authorSun, Tian‐tianen_US
dc.contributor.authorWeng, Yu‐rongen_US
dc.contributor.authorWang, Zhen‐huaen_US
dc.contributor.authorWang, Ji‐linen_US
dc.contributor.authorWang, Ying‐chaoen_US
dc.contributor.authorCui, Yunen_US
dc.contributor.authorSun, Dan‐fengen_US
dc.contributor.authorHan, Ze‐guangen_US
dc.contributor.authorShen, Nanen_US
dc.contributor.authorZou, Weipingen_US
dc.contributor.authorXu, Jieen_US
dc.contributor.authorChen, Hao‐yanen_US
dc.contributor.authorCao, Weibiaoen_US
dc.contributor.authorHong, Jieen_US
dc.contributor.authorFang, Jing‐yuanen_US
dc.date.accessioned2013-06-18T18:32:48Z
dc.date.available2014-09-02T14:12:52Zen_US
dc.date.issued2013-07en_US
dc.identifier.citationLin, Yan‐wei ; Ren, Lin‐lin ; Xiong, Hua; Du, Wan; Yu, Ya‐nan ; Sun, Tian‐tian ; Weng, Yu‐rong ; Wang, Zhen‐hua ; Wang, Ji‐lin ; Wang, Ying‐chao ; Cui, Yun; Sun, Dan‐feng ; Han, Ze‐guang ; Shen, Nan; Zou, Weiping; Xu, Jie; Chen, Hao‐yan ; Cao, Weibiao; Hong, Jie; Fang, Jing‐yuan (2013). "Role of STAT3 and vitamin D receptor in EZH2 â mediated invasion of human colorectal cancer." The Journal of Pathology 230(3): 277-290. <http://hdl.handle.net/2027.42/98269>en_US
dc.identifier.issn0022-3417en_US
dc.identifier.issn1096-9896en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/98269
dc.description.abstractThe polycomb group protein enhancer of zeste homologue 2 ( EZH2 ), which has histone methyltransferase ( HMT ) activity, is overexpressed in malignant tumours. However, the role of EZH2 in colorectal cancer ( CRC ) invasion is little known. Here we investigated the clinical significance, biological effects, and mechanisms of EZH2 signalling. Knockdown of EZH2 significantly reduced cell invasion and secretion of matrix metalloproteinases 2/9 ( MMP2 /9) in in vitro studies. Knockdown of EZH2 dramatically increased overall survival and decreased metastasis of lung in in vivo studies. Conversely, overexpression of EZH2 significantly increased lung metastasis and shortened overall survival when compared with control tumours. EZH2 ‐induced CRC cell invasion may depend on down‐regulation of vitamin D receptor ( VDR ), which is considered to be a marker of CRC invasion. EZH2 regulates the histone trimethylation of lysine 27 ( H3K27me3 ) in the VDR promoter. Moreover, we found that STAT3 directly binds to the EZH2 promoter and regulates VDR down‐regulation in CRC cells. Significant inverse correlations were observed between the expression of EZH2 and pSTAT3 and that of VDR in CRC tissues compared with normal tissue in patients. We show the role of EZH2 in CRC metastasis and identify VDR as a target gene of EZH2 . EZH2 expression may be directly regulated by STAT3 , and STAT3 may play an important role in EZH2 ‐mediated VDR down‐regulation in CRC . This pathway may provide potential targets in aggressive CRC . Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.en_US
dc.publisherJohn Wiley & Sons, Ltden_US
dc.subject.otherInvasionen_US
dc.subject.otherEZH2en_US
dc.subject.otherVitamin D Receptor, STAT3en_US
dc.subject.otherColorectal Canceren_US
dc.titleRole of STAT3 and vitamin D receptor in EZH2 ‐mediated invasion of human colorectal canceren_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelPathologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.identifier.pmid23424038en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/98269/1/path4179-sup-0004-FigureS3.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/98269/2/path4179-sup-0002-FigureS1.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/98269/3/path4179.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/98269/4/path4179-sup-0003-FigureS2.pdf
dc.identifier.doi10.1002/path.4179en_US
dc.identifier.sourceThe Journal of Pathologyen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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