MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling.
MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling.
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MiR-338-3p 通过靶向 ZEB2 和 MACC1/Met/Akt 信号传导抑制胃癌细胞的上皮间质转化
DOI：
10.18632/oncotarget.3835
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发表时间：
2015-06-20
期刊：
影响因子：
--
通讯作者：
Liao W
中科院分区：
文献类型：
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作者：
Huang N;Wu Z;Lin L;Zhou M;Wang L;Ma H;Xia J;Bin J;Liao Y;Liao W
MicroRNAs （miRNAs）参与了上皮-间质转化（EMT）过程，并与胃癌（GC）的转移有关。据报道，MiR-338-3p在GC中异常表达。在本研究中，我们发现miR-338-3p在体外抑制GC细胞的迁移和侵袭。在GC细胞中敲低miR-338-3p导致间质样改变。MiR-338-3p通过上调上皮标志物E-cadherin和下调间质标志物N-cadherin、纤连蛋白和vimentin来影响emt相关蛋白的表达。在机制上，miR-338-3p直接靶向锌指e盒结合蛋白2 （ZEB2）和结肠癌转移相关蛋白1 （MACC1）。MiR-338-3p在MACC1抑制后抑制Met/Akt通路。重新引入ZEB2和MACC1逆转了mir -338-3p诱导的EMT抑制。同样，在人GC组织样本中，miR-338-3p与ZEB2或MACC1的表达也呈负相关。综上所述，miR-338-3p通过靶向ZEB2和MACC1/Met/Akt信号通路抑制胃癌细胞的EMT进展。
MicroRNAs (miRNAs) are involved in the epithelial-mesenchymal transition (EMT) process and are associated with metastasis in gastric cancer (GC). MiR-338-3p has been reported to be aberrantly expressed in GC. In the present study, we show that miR-338-3p inhibited the migration and invasion of GC cells in vitro. Knocking down miR-338-3p in GC cells led to mesenchymal-like changes. MiR-338-3p influenced the expression of the EMT-associated proteins by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal markers, N-cadherin, fibronectin, and vimentin. In terms of mechanism, miR-338-3p directly targeted zinc finger E-box-binding protein 2 (ZEB2) and metastasis-associated in colon cancer-1 (MACC1). MiR-338-3p repressed the Met/Akt pathway after MACC1 inhibition. Reintroduction of ZEB2 and MACC1 reversed miR-338-3p-induced EMT suppression. Consistently, inverse correlations were also observed between the expression of miR-338-3p and ZEB2 or MACC1 in human GC tissue samples. In conclusion, miR-338-3p inhibited the EMT progression in GC cells by targeting ZEB2 and MACC1/Met/Akt signaling.