H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer

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• 作者：Masahisa Ohtsuka^a ; ¹ ; Hui Ling^a ; ¹ ; ^{hling@mdanderson.org} ; Cristina Ivan^a ; ^b ; Martin Pichler^a ; ^c ; Daisuke Matsushita^a ; Matthew Goblirsch^a ; Verena Stiegelbauer^c ; Kunitoshi Shigeyasu^d ; Xinna Zhang^b ; Meng Chen^a ; Fnu Vidhu^a ; Geoffrey A. Bartholomeusz^a ; Yuji Toiyama^e ; Masato Kusunoki^e ; Yuichiro Doki^f ; Masaki Mori^f ; Shumei Song^g ; Jillian R. Gunther^h ; Sunil Krishnan^h ; Ondrej Slabyⁱ ; Ajay Goel^d ; Jaffer A. Ajani^g ; Milan Radovich^j ; George A. Calin^a ; ^b ; ^{gcalin@mdanderson.org}
• 关键词：H19 ; RB1 ; E2F ; CDK8 ; β-Catenin ; Colorectal cancer
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：13
• 期：Complete
• 页码：113-124
• 全文大小：2943 K
• 卷排序：13

文摘

High H19 expression in primary tumors is an independent predictor of short overall survival in CRC patients. RB1-E2F and CDK8-β-catenin signaling are essential in mediating the oncogenic activity of H19 in CRC. Combined analysis of H19 and its targets further improved the prediction power on overall survival of CRC patients.Long noncoding RNAs (lncRNAs) are transcripts at least 200 nucleotides long that do not code for proteins. The clinical relevance of lncRNAs in colorectal cancer (CRC) is largely unknown. Here we identified that H19 expression in primary tumors is an independent prognostic predictor of poor prognosis of CRC patients and further proved its oncogenic role. To characterize the mechanisms, we profiled gene expression changes following H19 modulation in CRC cell lines and analyzed gene expression association in clinical datasets. Our data revealed important cancer-signaling pathways, including the RB1-E2F and the CDK8-β-catenin signaling, underlying H19 function.