Suppression of miR-4735-3p in androgen receptor-expressing prostate cancer cells increases cell death during chemotherapy.

MicroRNAs (miRNAs) play critical roles in the tumorigenesis of prostate cancer, while the biological function of miR-4735-3p is unknown. Mitogen-activated protein kinase kinase kinase 1 (MEKK1) has been shown to induce androgen receptor (AR)-dependent apoptosis in prostate cancer cells, but the regulation of MEKK1 in prostate cancer cells remains poorly defined. Here, we showed that miR-4735-3p was a MEKK1-targeting miRNA, and was highly expressed in AR+ prostate cancer specimens. Moreover, the levels of miR-4735-3p and MEKK1 inversely correlated. MiR-4735-3p-low subjects had a better overall survival, compared to miR-4735-3p-high subjects. MiR-4735-3p targeted the 3'-UTR of MEKK1 mRNA to inhibit its protein translation. Overexpression of miR-4735-3p inhibited MEKK1-mediated cell apoptosis upon docetaxel treatment, while depletion of miR-4735-3p enhanced it. Together, our data suggest that miR-4735-3p may suppress MEKK1-mediated prostate cancer cell apoptosis during chemotherapy. Inhibition of miR-4735-3p may improve the outcome of chemotherapy for some prostate cancers.