18β-glycyrrhetinic Acid Suppresses Gastric Cancer by Activation of MiR-149-3p-Wnt-1 Signaling

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Oct 8

PMID 27713126

Citations 27

Authors

Donghui Cao

Zhifang Jia

Lili You

Yanhua Wu

Zhen Hou

Yueer Suo

Houjun Zhang

Simin Wen

Tetsuya Tsukamoto

Masanobu Oshima

Jing Jiang

Xueyuan Cao

Affiliations

Soon will be listed here.

Abstract

18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer.

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