Mir - 205 On Proliferation Of Prostate Cancer And Transfer Function And Molecular Mechanism Research On The Effects Of Learning

Objectives: Prostate cancer (PCa) is characterized by deregulated expression ofseveral tumor suppressor or oncogenic miRNAs. Recent data have showed thatmiRNAs play an essential role in tumor proliferation and metastasis. The purpose ofthis study was to elucidate the molecular and functional mechanisms by whichhas-miR-205acts as a tumor suppressor in PCa.Methods: We examined the miRNAs expression profiles of early PCa andadvanced PCa tissues by miRNAs microarray analysis. Real-time quantitative reversetranscriptase polymerase chain reaction (qRT-PCR) was performed to detect theexpression level of miR-205in primary samples. Then, the effects of miR-205downregulation on proliferation, colony formation, cell cycle, apoptosis, migration,invasion and tumor formation of PCa cells were investigated. In addition, luciferasereporter assay was used to determine v-src sarcoma (Schmidt-Ruppin A-2) viraloncogene homolog (c-SRC) as a target of miR-205. Finally, the levels of c-SRC,p-c-SRC, focal adhesion kinase (FAK), p-FAK, extracellular signal-regulated kinase(ERK)1/2, p-ERK, c-MYC and CYCLIND1were measured by Western blottinganalysis.Results: The expression of miR-205significantly decreased in advanced PCacompared with early PCa by miRNAs microarray analysis. We further found thatmiR-205expression was significantly decreased in PCa tissues compared tononcancerous tissues using real-time PCR analysis. Moreover, the expression ofmiR-205was demonstrated to be associated with clinicopathological stage andtotal/free PSA level of PCa. Functional analyses showed that both overexpression ofmiR-205and knockdown of c-src in PCa cell lines inhibited cell growth, colony formation, migration, invasion, cell cycle and induced cell apoptosis in vitro.Moreover, overexpression of miR-205reduced tumorigenicity in vivo. Using aluciferase activity assay and western bloting, c-src was identified as a target ofmiR-205in cells. Overexpression of miR-205suppressed c-SRC and its downstreamsignaling molecules such as FAK, p-FAK, ERK1/2and p-ERK1/2expression.Conclusions: Our results demonstrate that miR-205is downregulated inPCa,functions as a tumor suppressor and directly regulates cell proliferation andmetastasis by targeting c-src. These findings also suggest that miR-205may be apotential therapeutic target in PCa.