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

// Donghui Cao 1 , Zhifang Jia 1 , Lili You 1 , Yanhua Wu 1 , Zhen Hou 2 , Yueer Suo 2 , Houjun Zhang 2 , Simin Wen 1 , Tetsuya Tsukamoto 3 , Masanobu Oshima 4 , Jing Jiang 1 , Xueyuan Cao 2 1 Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China 2 Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China 3 Department of Diagnostic Pathology I, School of Medicine, Fujita Health University, Toyoake, 470-1192, Japan 4 Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan Correspondence to: Jing Jiang, email: jiangjing19702000@jlu.edu.cn Xueyuan Cao, email: caoxy@aliyun.com Keywords: 18β-glycyrrhetinic acid, gastric cancer, COX-2, miR-149-3p, Wnt-1 Received: May 05, 2016      Accepted: September 24, 2016      Published: October 04, 2016 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.