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

Denglong Wu,Jun Xiang,Shengsong Huang,Cuidong Bian,Hao Wang

doi:10.1186/s13046-015-0125-x

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.

Highlights

Prostate cancer is the most frequent malignancy among men in most developed countries, and it was estimated to contribute to 28% of newly diagnosed cancers and 11% of cancer-related deaths in 2011 [1]
MiR-203 is aberrantly expressed in human prostate cancer tissues and cell lines Previous reports have shown that miR-203 was reduced in primary prostate cancer and even more reduced in metastatic PCa
We found that miR-203 was significantly down-regulated in carcinoma tissues compared with the matched adjacent non-tumor tissues (P < 0.01; Figure 1A)

Summary

Introduction

Prostate cancer is the most frequent malignancy among men in most developed countries, and it was estimated to contribute to 28% of newly diagnosed cancers and 11% of cancer-related deaths in 2011 [1]. The etiology of prostate cancer is still unknown, growing evidence has indicated that multiple changes in specific genes in particular tumors are responsible for the development and progression of PCa [4,5,6,7]. The roles of miRNA have proven to be indispensable in affecting cancer biology, including proliferation, autophagy, apoptosis, and invasiveness [10,11,12,13,14]. Accumulating data have suggested that miRNAs are involved in the tumorigenesis and progression of prostate cancer and act as a tumor suppressors or oncogenes [15,16,17,18,19,20]. MiR-203, a putative tumor suppressor gene, has been shown to inhibit cell proliferation and invasion and modulate the chemotherapy

Methods

Results

Conclusion