miR-375-3p/YWHAZ/β-catenin axis regulates migration, invasion, EMT in gastric cancer cells
miR-375-3p/YWHAZ/β-catenin axis regulates migration, invasion, EMT in gastric cancer cells
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DOI：
10.1111/1440-1681.13047
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发表时间：
2019-02-01
影响因子：
2.9
通讯作者：
Jin, Chunxiang
中科院分区：
文献类型：
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作者：
Guo, Feng;Gao, Yongjian;Jin, Chunxiang
YWHAZ （14-3-3 zeta）在胃癌（GC）细胞增殖、凋亡、迁移、侵袭等调控中发挥重要作用。然而，其在GC细胞中的广泛作用和潜在机制尚不清楚，需要深入研究。在本研究中，我们重点研究了miR-375/YWHAZ轴在胃癌细胞迁移、侵袭和上皮-间质转化（EMT）中的作用。采用western blot和qPCR检测GC细胞中YWHAZ水平。采用划痕法和transwell法测定GC细胞的迁移和侵袭。western blot检测相关分子蛋白水平。通过双荧光素酶报告系统验证miR-375对其靶基因YWHAZ表达的调控作用。结果表明，敲低YWHAZ可抑制GC细胞的迁移、侵袭和EMT。此外，YWHAZ的沉默抑制了wnt/ β -catenin信号通路的激活。YWHAZ被证实是miR-375的靶基因，其在GC细胞中的表达受miR-375调控。转染miR-375 inhibitor可促进GC细胞的迁移、侵袭、EMT和wnt/ β -catenin通路的激活，而YWHAZ抑制了这些通路。综上所述，本研究提示miR-375/YWHAZ轴可能作为胃癌患者的一种新的治疗靶点。
YWHAZ (14-3-3 zeta) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR-375/YWHAZ axis in migration, invasion and epithelial-to-mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR-375 on the expression of its target gene YWHAZ was verified by dual-luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/beta-catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR-375, and its expression was regulated by miR-375 in GC cells. Transfection of miR-375 inhibitor promoted the migration, invasion, EMT and activation of wnt/beta-catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR-375/YWHAZ axis may be served as a novel therapeutic target for GC patients.