The following is a summary of “Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure,” published in the April 2024 issue of Urology by Wu et al.
A notable gap in current research lies in the exploration of how erastin, a compound with potential therapeutic implications for prostate cancer (PCa), exerts its effects on PCa cells, as well as the identification of pivotal ferroptosis-related genes (FRGs) that could serve as promising therapeutic targets for PCa treatment. To address this, our study employed a series of in vitro assays and utilized RNA sequencing to assess the expression levels of differentially expressed genes (DEGs) in PCa cells induced by erastin. Employing a comprehensive array of bioinformatic analyses, we scrutinized the pathways and DEGs associated with erastin exposure.
Our findings revealed that erastin effectively suppressed the expression of SLC7A11, a key component of ferroptosis regulation, consequently impacting cell survivability in LNCaP and PC3 cells. Furthermore, erastin treatment led to significant increases in malondialdehyde (MDA) and Fe2+ concentrations, while concurrently decreasing levels of glutathione (GSH) and oxidized glutathione (GSSG) in both cell lines. Notably, we identified 295 overlapping DEGs in response to erastin exposure, which exhibited significant enrichment in pathways such as DNA replication and cell cycle regulation. Additionally, erastin treatment resulted in a notable increase in the proportion of LNCaP and PC3 cells in the G1 phase of the cell cycle.
Our study further delineated the role of specific hub FRGs, highlighting TMEFF2 as a potential therapeutic target in PCa. Higher expression levels were observed in PCa tissue. Conversely, NRXN3, CLU, and UNC5B expression levels were diminished in PCa tissue. Intriguingly, knockdown of TMEFF2 in androgen-dependent PCa cell lines (LNCaP and VCaP) resulted in suppressed expression of SLC7A11 and decreased cell survivability, with a concomitant increase in Fe2+ concentration observed solely in these cells.
In conclusion, our study underscores TMEFF2 as a promising candidate for ferroptosis-targeted therapy in PCa, offering valuable insights into the intricate molecular mechanisms underlying erastin-induced alterations in PCa cells. Through elucidating these mechanisms, our research contributes to the expanding landscape of potential therapeutic avenues for PCa treatment.
Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01472-1