MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. In the present study, we demonstrated that the expression ofmiR-133a was dramatically decreased in examined esophageal squamous cell carcinoma (ESCC) cell lines and clinical ESCC tissue samples. Additionally, miR-133a expression was inversely correlated with tumor progression in ESCCs. We have found that over-expression of miR-133a significantly suppressed the proliferation, migration and invasion of ESCC cells in vitro. miR-133a over-expression also significantly suppressed the aggressive phenotype of ESCC in vivo, suggesting that miR-133a may function as a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was a direct target gene of miR-133a, evidenced by the direct binding of miR-133a with the 3'UTR of Sox4. Notably, the EMT marker E-cadherin or vimentin, a downstream of Sox4, was also down-regulated or upregulated upon miR-133a treatment. We have also shown that over-expressing or silencing Sox4 was able to elevate or inhibit the migration and invasion of ESCC cells, similar to the effect of miR-133a on the ESCC cells. Moreover, knockdown of Sox4 reversed the enhanced migration and invasion mediated by anti-miR-133a. These results demonstrate that miR-133a acts as a tumor suppressor in ESCC through targeting Sox4 and the EMT process. miR-133a may serve as a potential target in the treatment of human esophageal cancer.