18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.
18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.
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18β-甘草次酸通过激活 miR-149-3p-Wnt-1 信号传导抑制胃癌
DOI：
10.18632/oncotarget.12443
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Cao X
中科院分区：
文献类型：
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作者：
Cao D;Jia Z;You L;Wu Y;Hou Z;Suo Y;Zhang H;Wen S;Tsukamoto T;Oshima M;Jiang J;Cao X
18β-甘草酸（glycyrrhetinic acid， GRA）对多种癌症均有抗肿瘤作用。在本研究中，我们发现GRA减轻了转基因小鼠胃炎的严重程度，抑制了胃肿瘤的发生。我们还发现，与正常胃组织和上皮细胞相比，miR-149-3p在胃癌组织和细胞系中下调，而在GRA中上调。miR-149-3p的表达也与淋巴结转移呈负相关。我们的功能分析显示，miR-149-3p过表达抑制细胞增殖和细胞周期进程，同时诱导细胞凋亡，而抑制miR-149-3p则具有相反的作用。此外，我们发现Wnt-1是miR-149-3p的直接靶点。这些数据表明，GRA通过下调COX-2表达改善炎症微环境，通过上调肿瘤抑制因子miR-149-3p抑制Wnt-1表达，从而抑制胃肿瘤的发生和发展。因此，GRA可能具有作为预防和治疗胃癌的有用治疗剂的潜力。
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.