MicroRNA-539 Inhibits the Epithelial–Mesenchymal Transition of Esophageal Cancer Cells by Twist-Related Protein 1-Mediated Modulation of Melanoma-Associated Antigen A4

MicroRNAs (miRs) play key roles in cancers, yet the potential molecular mechanisms of miR-539 on esophageal squamous cell carcinoma (ESCC) are not well understood. Utilizing informatics screening, Twist-related protein 1 (TWIST1) was hypothesized to be a possible target gene of miR-539. Since the melanoma-associated antigen (MAGE) A4 is reported to be upregulated by TWIST1, this study aimed to examine the biological functions and mechanism involving TWIST1 and MAGE4 of miR-539 in ESCC. miR-539 mimics or scrambled miRs were transfected into human ESCC TE3 cells to interfere with the expression of miR-539. Then qRT-PCR and Western blot analyses were performed to determine the expression levels of epithelial–mesenchymal transition (EMT)-related factors at mRNA and protein levels. The association between miR-539 and TWIST1 as well as TWIST1 and MAGEA4 was evaluated. The connection of miR-539 and TWIST1–MAGEA4 during the EMT progress of ESCC was also explored. Our data demonstrated that miR-539 inhibited the EMT of TE3 cells by downregulating TWIST1, and TWIST1 was a target of miR-539. Moreover, MAGEA4 was positively correlated with TWIST1, and its knockdown inhibited EMT in TE3 cells. Collectively, miR-539 could inhibit EMT in TE3 cells through TWIST1-mediated regulation of MAGEA4. All these findings suggested that miR-539 may be involved in the progression of ESCC and could be a new therapeutic target for this disease.