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Pannexin 2 被确定为与铁死亡和前列腺癌细胞恶性表型相关的新型标志物
Authors Liao D, Yang G, Yang Y, Tang X, Huang H, Shao J, Pan Q
Received 14 February 2020
Accepted for publication 26 April 2020
Published 19 May 2020 Volume 2020:13 Pages 4411—4421
DOI https://doi.org/10.2147/OTT.S249752
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Leo Jen-Liang Su
Purpose: 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