miRNA-145 Transcriptionally Regulates Semaphorin 3a Expression in Prostate Cancer Cells

Abstract

Prostate cancer (PCa) is one of the most prevalent cancer types among males. Differential expression of microRNAs is associated with various cancers including PCa. Although mature microRNAs are preferentially located in the cytoplasm, several studies identified mature human microRNAs in purified nuclei and miR-145 has been found to be predominantly expressed in the nuclei of benign tissues compared to tumor lesions. However, the nuclear functions of miR-145 are yet limited. Here, we aimed at investigating the inductive role of miR-145 on the expression of Semaphorin 3A (SEMA3A) in PCa cell lines. To study the regulatory potential of miR-145 in the transcriptional level in PCa, we overexpressed miR-145 in PC3 and DU145 cells, and confirmed its upregulation by quantitative-real-time-PCR. Then we investigated the tumor suppressor potential of miR-145 upon inducing SEMA3A expression using cell viability assay, western blot analysis, Chromatin Immunoprecipitation assay and luciferase reporter assay. Our results revealed that p53, miR-145, and SEMA3A expressions are significantly downregulated in PC3 and DU145 cells compared to nontumorigenic prostate epithelial PNT1a cells. miR-145 overexpression in PCa cells induced the expression of SEMA3A at both messenger RNA and protein levels. Furthermore, increased miR-145 expression enriched RNA Pol-II antibody on the promoter of SEMA3A and induced luciferase activity controlled by SEMA3A promoter. In this study, we showed that the functions of miR-145 are not limited to gene silencing, and found that it may lead to changes in gene expression in the transcriptional level.