PMID- 30888515 OWN - NLM STAT- MEDLINE DCOM- 20190506 LR - 20200225 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 145 IP - 5 DP - 2019 May TI - TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer. PG - 1297-1311 LID - 10.1007/s00432-019-02898-z [doi] AB - PURPOSE: Transient 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. METHODS: Human 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. RESULTS: The 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. CONCLUSION: We 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. FAU - Tektemur, Ahmet AU - Tektemur A AUID- ORCID: 0000-0002-2476-0413 AD - Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey. atektemur@firat.edu.tr. FAU - Ozaydin, Seda AU - Ozaydin S AD - Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey. FAU - Etem Onalan, Ebru AU - Etem Onalan E AD - Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey. FAU - Kaya, Nalan AU - Kaya N AD - Department of Histology, Faculty of Medicine, Firat University, Elazig, Turkey. FAU - Kuloglu, Tuncay AU - Kuloglu T AD - Department of Histology, Faculty of Medicine, Firat University, Elazig, Turkey. FAU - Ozercan, Ibrahim Hanifi AU - Ozercan IH AD - Department of Medical Pathology, Faculty of Medicine, Firat University, Elazig, Turkey. FAU - Tekin, Suat AU - Tekin S AD - Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey. FAU - Elyas, Halit Mohammed AU - Elyas HM AD - Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey. LA - eng GR - TF.14.37/Firat University Scientific Research Projects Management Unit/ PT - Journal Article DEP - 20190319 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (TRPM Cation Channels) RN - 0 (TRPM2 protein, human) SB - IM MH - Apoptosis/genetics MH - Autophagy/*genetics MH - Cell Line, Tumor MH - Cell Survival/genetics MH - Gene Expression MH - Humans MH - Immunohistochemistry MH - Male MH - Neoplasm Grading MH - Prostatic Neoplasms/*etiology/*metabolism/pathology MH - RNA Interference MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - TRPM Cation Channels/*genetics/*metabolism OTO - NOTNLM OT - Autophagy OT - Gene expression OT - Ion channels OT - Prostate cancer OT - Transient receptor potential melastatin 2 (TRPM2) EDAT- 2019/03/20 06:00 MHDA- 2019/05/07 06:00 CRDT- 2019/03/20 06:00 PHST- 2019/01/02 00:00 [received] PHST- 2019/03/13 00:00 [accepted] PHST- 2019/03/20 06:00 [pubmed] PHST- 2019/05/07 06:00 [medline] PHST- 2019/03/20 06:00 [entrez] AID - 10.1007/s00432-019-02898-z [pii] AID - 10.1007/s00432-019-02898-z [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2019 May;145(5):1297-1311. doi: 10.1007/s00432-019-02898-z. Epub 2019 Mar 19.