TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer

摘要

PurposeTransient receptor potential melastatin 2 (TRPM2), a calcium-permeable ion channel, is shown as a prognostic marker candidate in prostate cancer (PCa) and an important regulator of autophagy. We aimed to determine the changes in TRPM2 and autophagic-apoptotic gene expression levels in human prostate adenocarcinomas, and to investigate the affect of TRPM2 on autophagic pathways in PC-3 cell line.MethodsHuman prostate tissues were classified considering the grade levels and were divided into the control, BPH, and grade 1-5 groups. mRNA expression levels of genes were determined by qPCR. In addition, TRPM2 was evaluated immunohistochemically for each group. In PC-3 cell line, TRPM2 was silenced through siRNA transfection, and autophagy induction was analyzed by acridine orange (AO) staining.ResultsThe qPCR and immunoreactivity results showed that the increased TRPM2 expression levels in human PCa samples were paralleled with higher grade levels. The autophagic-apoptotic gene expressions showed high variability in different grade levels. Also, silencing TRPM2 in PC-3 cells altered autophagic gene expressions and caused autophagy induction according to the AO staining results.ConclusionWe showed that the autophagy-TRPM2 association may take place in the molecular basis of PCa and accordingly this connection may be targeted as a new therapeutic approach in PCa.