OncoTargets and Therapy (May 2020)
Identification of Pannexin 2 as a Novel Marker Correlating with Ferroptosis and Malignant Phenotypes of Prostate Cancer Cells
Abstract
Duwu Liao,1,* Guang Yang,2,* Yuan Yang,3,* Xueyong Tang,4,* Haixia Huang,5 Jichun Shao,1 Qi Pan4 1Department of Urology Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, People’s Republic of China; 2Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 5Department of Critical Care Medicine, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jichun ShaoDepartment of Urology Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation, 416 Hospital, 4# Second Ring Road, North Fourth Section, Chengdu, Sichuan 610057, People’s Republic of ChinaEmail [email protected] PanDepartment of Dermatology, Chongqing Traditional Chinese Medicine Hospital, 40# Daomenkou, Yuzhong District, Chongqing 400011, People’s Republic of ChinaEmail [email protected]: Prostate cancer (PCa) is a widespread urinary neoplasm and one of the most prevalent and second most frequent malignancies diagnosed in males worldwide. This study aimed to identify a candidate marker and explore its molecular mechanism in PCa.Methods: Gene expression datasets, GSE55945 (n=21) and GSE46602 (n=50), were downloaded from the Gene Expression Omnibus database. Bioinformatic approaches were applied to identify potential markers. Effects of the candidate marker on proliferation, migration, invasion, and ferroptosis (ferrous iron and malondialdehyde (MDA)) in PCa cells and its mechanism were assessed after performing cell transfection.Results: A total of 1435 common differentially expressed genes were identified in GSE55945 and GSE46602. Five key gene modules were listed based on a protein–protein interaction network, containing five hub genes. Pannexin 2 (PANX2), a candidate marker was identified, and findings revealed substantial upregulation of its expression levels in PCa cell lines. Blocking expression of PANX2 resulted in suppression of proliferation, migration, and invasion in PCa cells, while increasing ferrous iron and MDA levels. However, these effects were rescued by Nrf2 activator, oltipraz. The Nrf2 signaling pathway was consequently applied to determine underlying mechanism of PANX2 in PCa cells. We established that silencing PANX2 remarkably reduced protein expression levels in members of Nrf2 signaling pathway (Nrf2, HO-1, and FTH1).Conclusion: Our study demonstrated that PANX2 is implicated in the pathogenesis of PCa, which regulates malignant phenotypes and ferroptosis through Nrf2 signaling pathway, and maybe a potential therapeutic target for PCa.Keywords: prostate cancer, ferroptosis, PANX2 and Nrf2 signaling pathways
