Open Access

ARTICLE

Long Noncoding RNA H19-Derived miR-675 Enhances Proliferation and Invasion via RUNX1 in Gastric Cancer Cells

by

* Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
† Department of Clinical Laboratory Center, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China
‡ Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China

Oncology Research 2015, 23(3), 99-107. https://doi.org/10.3727/096504015X14496932933575

Abstract

The lncRNA H19 and its mature product miR-675 have recently been shown to be upregulated and promote the progression of gastric cancer. However, the detailed function and underlying molecular mechanism of H19/miR- 675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that H19 depended on miR- 675 to enhance the proliferation and invasion of gastric cancer AGS cells, and the expression of miR-675 was positively correlated with H19 in patients with gastric cancer. Subsequently, the tumor-suppressor runt domain transcription factor 1 (RUNX1) was confirmed to be a downstream molecule of H19/miR-675 axis, since overexpression of H19 or miR-675 significantly decreased RUNX1 expression in AGS cells, and knockdown of H19 or miR-675 enhanced RUNX1 expression. More importantly, a series of assays further demonstrated that introduction of RUNX1 abrogated H19/miR-675-induced Akt/mTOR pathway activation and the following cellular proliferation and invasion of AGS cells. To our knowledge, this is the time to demonstrate that RUNX1 serves as a link between H19/miR-675 axis and Akt/mTOR signaling and is a pivotal mediator in gastric cancer progression induced by H19/miR-675. Thus, our study provides important clues for understanding the key roles of lncRNA-miRNA functional network and identifying new therapeutic targets for gastric cancer.

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Keywords

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