Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer

Oncotarget
Swati DharAnait S Levenson

Abstract

In recent years, not only has the role of miRNAs in cancer become increasingly clear but also their utilization as potential biomarkers and therapeutic targets has gained ground. Although the importance of dietary stilbenes such as resveratrol and pterostilbene as anti-cancer agents is well recognized, our understanding of their miRNA-targeting capabilities is still limited. In our previous study, we reported that resveratrol downregulates PTEN-targeting members of the oncogenic miR-17 family, which are overexpressed in prostate cancer. This study investigates the resveratrol and pterostilbene induced miRNA-mediated regulation of PTEN in prostate cancer. Here, we show that both compounds decrease the levels of endogenous as well as exogenously expressed miR-17, miR-20a and miR-106b thereby upregulating their target PTEN. Using functional luciferase reporter assays, we demonstrate that ectopically expressed miR-17, miR-20a and miR-106b directly target PTEN 3'UTR to reduce its expression, an effect rescued upon treatment with resveratrol and pterostilbene. Moreover, while stable lentiviral expression of miR-17/106a significantly decreased PTEN mRNA and protein levels and conferred survival advantage to the cells, resveratrol and ...Continue Reading

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Citations

Feb 28, 2020·Experimental and Therapeutic Medicine·Zheng XiaoXi Zeng
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Datasets Mentioned

BETA
GSE21036

Methods Mentioned

BETA
PCR
xenografts
xenograft
Assay
transfection

Software Mentioned

ImageTool
TargetScan
Diana
Image J
miRnome
MicroCosm
GEO query package
microT
CDS
MS Excel

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