MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer

• DOI: 10.4161/cbt.7.8.6284
• Publication Date: 2010-05-26T14:33:20Z
• Authors: Oskar W Rokhlin; Vladimir S Scheinker; Agshin F Taghiyev; David Bumcrot; Rebecca A Glover; Michael B. Cohen
• Keywords: DU145; Camptothecin

AbstractWe investigated whether knocking down AR expression effects apoptosis after treatment with different apoptosis-inducing agents. We found that siRNA (si-AR) significantly decreased induced by topoisomerase inhibitors doxorubicin (DOX) and camptothecin (Campt). It is known DNA double-strand break inducing agents leads to activation (phosphorylation) of p53 in turn regulates the a variety apoptosis-related genes including microRNA(miR)-34a 34b/c. DOX 5 phosphorylation sites (Ser15, 20, 37, 46, 392); all these were inhibited si-AR. Subsequently we identified three kinases, SPAK, MDC1, CaMKII are under control two them, MDC1 CaMKII, apparently participate upstream events resulted inhibition. Using qPCR showed level miR-34a increased 3-fold DOX, but no increase was MiR-34c 27 fold only 2.7 times appears AR-dependent inhibition suppression -34c expression. Importantly, did not induce miR-34 LNCaP grown an androgen free medium or AR-negative prostate cancer cell lines, DU145 PC3. To directly investigate role DOX-mediated apoptosis, transfected cells anti-miR-34 oligonucleotides miR-34. individual miR-34, either 34a 34c, forced over miR-34c modulate apoptosis. Only simultaneous both modulation Taken together, our data indicate cooperation between 34c plays important p53-mediated cancer.