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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #340523

Research Project: Health-Promoting Bioactives and Biobased Pesticides from Medicinal and Herbal Crops

Location: Natural Products Utilization Research

Title: Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer

Author
item KUMAR, AVINASH - Long Island University
item Vacant, Vacant
item LEVENSON, ANAIT - Long Island University

Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2017
Publication Date: 6/29/2017
Citation: Kumar, A., Rimando, A.M., Levenson, A.S. 2017. Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer. Annals of the New York Academy of Sciences. 1403(1):15-26.
DOI: https://doi.org/10.1111/nyas.13372

Interpretive Summary: RNAs (ribonucleic acids) are huge polymeric molecules in the cells that play a major role in controlling protein synthesis. There is a subset of small RNA molecules called microRNA that do not participate in protein synthesis. Growing evidence indicates the network of microRNAs (miRNAs) as a critical factor in the progression of various diseases including cancer. Polyphenols have been increasingly studied for their health effects that are mediated through miRNAs. Non-invasive detection of changes in miRNA expression in liquid biopsies opens enormous possibilities for their clinical utilization as novel prognostic and predictive biomarkers. In our studies, we have identified resveratrol-regulated miRNA profiles in prostate cancer. Resveratrol downregulated members of a family of miRNAs that are overexpressed in prostate cancer, which are targeted by the tumor suppressor protein called PTEN. We have validated the miRNA-mediated ability of resveratrol and its potent analog pterostilbene to rescue the tumor suppressor activity of PTEN both in vitro and in vivo. Taken together, our findings implicate the use of resveratrol and its analogs as attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer, and circulating miRNAs as potential predictive clinical biomarkers.

Technical Abstract: Growing evidence indicates deregulation of the epigenetic machinery comprising the microRNA (miRNA) network as a critical factor in the progression of various diseases including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA-mediated health beneficial properties such as anti-inflammatory, cardioprotective, antioxidative, and anticancer. Available experimental data have suggested that dietary polyphenols may be effective miRNA-modulating chemopreventive and therapeutic agents. Moreover, non-invasive detection of changes in miRNA expression in liquid biopsies opens enormous possibilities for their clinical utilization as novel prognostic and predictive biomarkers. In our studies, we have identified resveratrol-regulated miRNA profiles in prostate cancer. Resveratrol downregulated the PTEN-targeting members of oncogenic miR-17 family of miRNAs, which are overexpressed in prostate cancer. We have functionally validated miRNA-mediated ability of resveratrol and its potent analog pterostilbene to rescue the tumor suppressor activity of PTEN in vitro and in vivo. Taken together, our findings implicate the use of resveratrol and its analogs as attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer, and circulating miRNAs as potential predictive biomarkers for clinical development.