18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling

Donghui Cao, Zhifang Jia, Lili You, Yanhua Wu, Zhen Hou, Yueer Suo, Houjun Zhang, Simin Wen, Tetsuya Tsukamoto, Masanobu Oshima, Jing Jiang, Xueyuan Cao

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)71960-71973
Number of pages14
JournalOncotarget
Volume7
Issue number44
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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