Published on June 28, 2016 in Cancer Lett volume 376(1).

PubMed ID: 26996300

DOI: S0304-3835(16)30076-3

Abstract:

YTH domain containing 2 (YTHDC2) is a member of the DExD/H-box family ofATP-dependent RNA helicases. We previously found that YTHDC2 expression isup-regulated in several human cancer cells. In this study, we demonstrate novelroles for YTHDC2 in metastasis of colon tumor cells via translation-dependentpathway. Knockdown of YTHDC2 attenuated protein expression of metastasis-relatedgenes, such as hypoxia-inducible factor-1alpha (HIF-1α), and inhibited metastasis ofcolon tumor cells in vitro and in vivo. To confirm that YTHDC2 promotes translationinitiation by unwinding the 5'-untranslated region (5'UTR) of mRNA, we constructed afirefly luciferase reporter containing the 5'UTR of the HIF-1α mRNA and showedreduction in luciferase activity in YTHDC2-silenced cells. Furthermore, we examinedexpression levels of YTHDC2 by immunohistochemical staining in human colon cancertissues from 72 patients and found a significantly positive correlation betweenYTHDC2 expression and the tumor stage, including metastasis. In conclusion, theseresults suggest that the RNA helicase YTHDC2 contributes to colon tumor metastasisby promoting translation of HIF-1α and that YTHDC2 is potentially a diagnosticmarker and target gene for treating colon cancer patients.CI - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.