Resveratrol and prostate cancer: Promising role for microRNAs

SCOPE: Resveratrol (Res) has anticancer activity in prostate cancer (PCa), which can be attributed to modulation of microRNAs (miRNAs/miRs). miRNAs/miRs are small non-coding RNAs that negatively regulate gene expression. We have analyzed differential miRNA expression in PCa cells treated with Res. METHODS AND RESULTS: Using miRNA microarrays we found that 23 miRNAs were significantly down-regulated and 28 miRNAs were significantly up-regulated after Res treatment. The down-regulated miRs included miR-17-92 and miR-106ab clusters with well recognized oncogenic properties while the up-regulated miRs included several tumor suppressors. Selected miRs were verified by qRT-PCR, including miR-17, miR-20a, miR-20b, miR-106a and miR106b. Since these miRNAs target PTEN (phosphatase and tensin homolog deleted on chromosome 10), we performed Western blot to confirm up-regulation of PTEN in PCa cells. In addition, using TargetScan database, we have identified putative mRNA targets for Res-induced down- and up-regulated miRs. Using a bioinformatics approach, we generated gene networks specifically altered by Res-regulated miRNAs. CONCLUSION: Our results indicate that the dietary compound Res may play an important role in prostate carcinogenesis through modulation of miRNA expression: Res down-regulated oncogenic miRs and up-regulated tumor suppressor miRs in PCa cells. Further in-depth studies are necessary in order to fully recognize the beneficial miRNA-mediated effects of Res in PCa.