Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1290-1296. doi: 10.26355/eurrev_201803_14470.
Emerging evidence suggests aberrant microRNAs (miRNAs) expression is involved in cancer development through multiple. Although miR338 has shown to have tumor suppression ability and anti-migration effects in some cancers, its regulatory role and molecular mechanism in the development of gastric cancer cells yet remains little known. This work aims to investigate miR-338 in regulating Wnt/β-catenin pathway in epithelial-mesenchymal transition (EMT) in gastric cancers.
Human gastric cancer cells were transfected with either miR-338 mimic or erythropoietin-producing hepatocellular (Eph)A2-targeting siRNA. The biological function of miR-338 in gastric cancer cells was investigated using a MTT assay and invasion assay. Western blot assay was used to measure the levels of EphA2, GSK-3β, phospho-GSK-3βSer9, c-Myc, E-cadherin, Vimentin, and β-catenin of at protein level.
Our data showed that miR-338 inhibited proliferation, migration and invasion of human gastric cancer cells. miR-338 affected the Wnt/β-catenin pathway by increasing p-GSK-3βSer9 and decreasing GSK-3βSer9 and c-Myc at protein levels. EphA2 protein level was downregulated and positively correlated with EMT markers. Both silencing of EphA2 and transfection with miR-338 mimic resulted in the up-regulation of the EMT molecular marker E-cadherin and down-regulation of Vimentin and β-catenin at protein levels.
This study indicated that miR-338 is a potential tumor suppressor in gastric cancer and miR-338 inhibited EMT of gastric cancer cells through deactivation of Wnt/β-catenin signaling targeting at EphA2.
新出现的证据表明，异常的 microRNAs（miRNAs）表达通过多种途径参与癌症的发生。虽然 miR338 在一些癌症中显示出具有肿瘤抑制能力和抗迁移作用，但它在胃癌细胞发展中的调节作用和分子机制知之甚少。本研究旨在探讨 miR-338 在调节胃癌上皮-间充质转化（EMT）中的 Wnt/β-catenin 通路中的作用。
用人胃癌细胞转染 miR-338 模拟物或促红细胞生成素产生肝细胞（Eph）A2 靶向 siRNA。通过 MTT 测定和侵袭测定研究 miR-338 对胃癌细胞的生物学功能。Western blot 测定用于测量 EphA2、GSK-3β、磷酸化 GSK-3βSer9、c-Myc、E-钙粘蛋白、波形蛋白和β-catenin 的蛋白水平。
我们的数据表明，miR-338 抑制人胃癌细胞的增殖、迁移和侵袭。miR-338 通过增加 p-GSK-3βSer9 和降低 EphA2 蛋白水平来影响 Wnt/β-catenin 通路，进而降低 GSK-3βSer9 和 c-Myc。EphA2 蛋白水平下调，并与 EMT 标志物呈正相关。EphA2 沉默和 miR-338 模拟物转染均导致 EMT 分子标志物 E-钙粘蛋白上调，波形蛋白和β-catenin 下调。
本研究表明，miR-338 是胃癌的潜在肿瘤抑制因子，通过靶向 EphA2 失活 Wnt/β-catenin 信号通路，miR-338 抑制胃癌细胞 EMT。
