The biological functions and mechanism of miR-212 in prostate cancer proliferation, migration and invasion via targeting Engrailed-2

Accumulating evidence indicates that Engrailed-2 (EN-2), which is a homeobox-containing transcription factor, act as a candidate oncogene in prostate cancer (PCa). Even though there are some treatments targeting EN-2, however, it is limited because the mechanism of EN-2 upregulation in PCa cells is still unknown. In this study, we investigate the role of miR-212 on EN-2 expression and explored the mechanism of prostate cancer survival and metastasis. The relative expression levels of miR-212 and EN-2 in PCa samples and adjacent normal tissues as well as in PCa cell lines were detected by using quantitative real-time PCR. CCK-8, TUNEL and Transwell assays were used to analyze cell proliferation, apoptosis and invasion, respectively. EN-2 was identified as a direct target of miR-212 via luciferase reporter and western blot assays. Results showed that the expression level of miR-212 was downregulated in both PCa samples and PCa cell lines when compared with prostate epithelial cells and the adjacent no tumor tissues. Moreover, we found that overexpression of miR-212 suppressed PCa cell proliferation and invasion, promoted PCa cell apoptosis. EN-2 was identified as a direct target gene of miR-212 by using luciferase reporter and western blot assays. Also, the expression of EN-2 and miR-212 in the PCa cells had an opposite correlation. The critical role of miR-212 in inhibiting prostate tumor growth was verified in xenograft models of prostate cancer. These findings highlighted the role of miR-212 in PCa progression. More importantly, we speculate that EN-2 is a direct target gene of miR-212.