(−)-Epigallocatechin-3-gallate suppresses prostate cancer cell growth via activating miR-520a-3p

REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY(2020)

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摘要
Prostate cancer is the 2nd most common cancer affecting the male population. Polyphenols such as (−)-epigallocatechin-3-gallate (EGCG) from green tea carry biological benefits against prostate cancer. But the molecular mechanism underlying its protective function is not fully understood. The study was aimed to characterize a novel microRNA that plays an important role in this pathway. First, we measured miR-520a-3p expressional response to four green tea polyphenols. Next, we studied its expression and functional impact in prostate cancer lines. Then, we characterized AKT1 as its downstream target with luciferase reporter assay and Western blot analysis. We also employed miR-520a-3p inhibitor to conform this signaling axis in functional inhibition of cancer cells. Last, we evaluated miR-520a-3p expressional change in clinical cancer samples. We showed miR-520a-3p was downregulated in cancer cells. EGCG among the four polyphenols exhibited the highest levels of cancer cells’ inhibition and miR-520a-3p induction. The upregulation of miR-520a-3p inhibited cancer cells through downregulating AKT1. MiR-520a-3p inhibitor confirmed this novel pathway in EGCG-mediated cancer cells’ inhibition. Finally, clinical study suggested miR-520s-3p was downregulated in prostate cancer. Our study concluded EGCG confers its protection function against prostate cancer through activating miR-520a-3p, revealing new intervention targets for managing prostate cancer. Graphical abstract
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关键词
Green tea extract, EGCG, miR-520a-3p, AKT1, Prostate cancer
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