TY - JOUR
T1 - 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling
AU - Cao, Donghui
AU - Jia, Zhifang
AU - You, Lili
AU - Wu, Yanhua
AU - Hou, Zhen
AU - Suo, Yueer
AU - Zhang, Houjun
AU - Wen, Simin
AU - Tsukamoto, Tetsuya
AU - Oshima, Masanobu
AU - Jiang, Jing
AU - Cao, Xueyuan
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (no. 81273065 and no. 81072369) and the Norman Bethune Program of Jilin University (no. 2013025).
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84995505915
UR - https://www.scopus.com/pages/publications/84995505915#tab=citedBy
U2 - 10.18632/oncotarget.12443
DO - 10.18632/oncotarget.12443
M3 - Article
C2 - 27713126
AN - SCOPUS:84995505915
SN - 1949-2553
VL - 7
SP - 71960
EP - 71973
JO - Oncotarget
JF - Oncotarget
IS - 44
ER -
