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

Varování

Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	OHTSUKA Masahisa LING Hui IVAN Cristina PICHLER Martin MATSUSHITA Daisuke GOBLIRSCH Matthew STIEGELBAUER Verena SHIGEYASU Kunitoshi ZHANG Xinna CHEN Meng VIDHU Fnu BARTHOLOMEUSZ Geoffrey A. TOIYAMA Yuji KUSUNOKI Masato DOKI Yuichiro MORI Masaki SONG Shumei GUNTHER Jillian R. KRISHNAN Sunil SLABÝ Ondřej GOEL Ajay AJANI Jaffer A. RADOVICH Milan CALIN George A.
Rok publikování	2016
Druh	Článek v odborném periodiku
Časopis / Zdroj	EBioMedicine
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.sciencedirect.com/science/article/pii/S235239641630487X
Doi	http://dx.doi.org/10.1016/j.ebiom.2016.10.026
Obor	Onkologie a hematologie
Klíčová slova	H19; RB1; E2F; CDK8; beta-Catenin; Colorectal cancer
Popis	The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and beta-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of beta-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Související projekty:	CEITEC 2020