MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling

Abstract

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.

The expression of metastasis-associated in colon cancer-1 and KAI1 in gastric adenocarcinoma and their clinical significance

“…Furthermore, MACC1 expression was positively correlated with tumor size, grade, invasion of depth, LNM, and TNM stage. Our results were consistent with those of previous studies in GAC [8, 31–33] demonstrating that MACC1 should be useful as a clinical candidate biomarker of GAC.…”

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

“…The expression of ZEB2 has been reported in different tumors, including bladder cancer [30,31]. Recent reports highlighted that ZEB2 was closed related to EMT [32,33], suggesting ZEB2 is a key factor in promoting the initiation and development of cancer. It was reported that ZEB2 led to the loss of epithelial marker E-cadherin and disrupt cell-to-cell adhesion.…”

Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2

“…ZEB2 is the second family member and described as a factor collaborating with the TGF-b signaling pathway by interacting with SMAD factors and promotes tumor cell invasion [16][17][18]. Reports showed that ZEB2 could be regulated by miR-139-5p in HCC which inhibits EMT and metastasis [21], miR-338-3p in gastric cancer cells which inhibits EMT [22], miRNA-200a in HCC suppresses metastatic potential of side population cells [23], miR-132 in lung cancer suppresses the migration and invasion [24] and others [25,26]. In HCC, there are other miRNAs like miR-132 and miR-206 which could inhibit hepatocellular carcinoma cell proliferation, metastasis and promote apoptosis of hepatocellular carcinoma [27,28].…”