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.