MiR-203 down-regulates Rap1A and suppresses cell proliferation, adhesion and invasion in prostate cancer

Abstract

ObjectiveEvidence supports an important role for miR-203 in the regulation of the proliferation, migration and invasion of prostate cancer (PCa) cells. However, the exact mechanisms of miR-203 in PCa are not entirely clear.MethodsWe examined the expression of miR-203 in prostate cancer tissues, adjacent normal tissues, PCa cell lines and normal prostate epithelial cells by qRT-PCR. Then, the effects of miR-203 or Rap1A on proliferation, adhesion and invasion of PCa cells were assayed using CKK-8, adhesion analysis, and transwell invasion assays. Luciferase reporter assay was performed to assess miR-203 binding to Rap1A mRNA. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice.ResultsHere, we confirmed that the expression of miR-203 was significantly downregulated in prostate cancer specimens compared with matched adjacent normal prostate specimens. Mechanistic dissection revealed that miR-203 mediated cell proliferation, adhesion and invasion in vitro, and tumor growth in vivo, as evidenced by reduced RAC1, p-PAK1, and p-MEK1 expression. In addition, we identified Rap1A as a direct target suppressed by miR-203, and there was an inverse relationship between the expression of miR-203 and Rap1A in PCa. Knockdown of Rap1A phenocopied the effects of miR-203 on PCa cell growth and invasion. Furthermore, Rap1A over-expression in PCa cells partially reversed the effects of miR-203-expression on cell adhesion and invasion.ConclusionsThese findings provide further evidence that a crucial role for miR-203 in inhibiting metastasis of PCa through the suppression of Rap1A expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0125-x) contains supplementary material, which is available to authorized users.

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“…miR-203 is dysregulated in several cancers and it links to the tumor progression. For example, miR-203 is significantly downregulated in prostate cancer and renal cancer, and functions as a tumor suppressor by inhibiting cell proliferation, migration and invasion [38][39]. In studies of colorectal cancer, high levels of miR-203 were detected in CRC [40][41][42] and increased expression of miR-203 significantly inhibited proliferation, motility, as well as invasion of CRC cells [43], which is consistent with our data.…”

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