Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins.

Abstract

We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients. We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting. We found that treatment of prostate cancer cells with miR-139 resulted in phenotypic changes characteristic of autophagic cells. MiR-139 increased the autophagy-related conversion of the microtubule-associated protein light chain 3 (LC3-I to LC3-II) that was specifically inhibited by the miR-139 antagomir. The upregulation of LC3 II was further confirmed by confocal microscopy. miR-139 regulated activation of both mTOR and Beclin1 the two important autophagy-related molecules. We found that upon miR-139 treatment, the cargo adaptor protein p62 which is degraded during autophagy, accumulates. These results suggest that miR-139 is inducing autophagic flux blockade leading to apoptosis in prostate cancer cells through the mTOR and Beclin-1 proteins.