LincHOTAIR Epigenetically Silences MiR34a by Binding to PRC2 to Promote the Epithelial-to-mesenchymal Transition in Human Gastric Cancer

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2015 Jul 3

PMID 26136075

Citations 120

Authors

Y-W Liu

M Sun

R Xia

E-b Zhang

X-H Liu

Z-H Zhang

T-p Xu

W De

B-r Liu

Z-X Wang

Affiliations

Soon will be listed here.

Abstract

lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.

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