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Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure
Fan Wu1,2, Fei Huang1,2, Nili Jiang3
1Department of Biochemistry and Molecular Biology, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning, China.
Background:
Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known.
Methods:
In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs.
Results:
Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were identified under erastin exposure and significantly enriched in several pathways, including DNA replication and cell cycle. The percentage of LNCaP and PC3 cells in G1 phase was markedly increased in response to erastin treatment. For four hub FRGs, TMEFF2 was higher in PCa tissue and the expression levels of NRXN3, CLU, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in androgen-dependent cell lines (LNCaP and VCaP) but not in androgen-independent cell lines (PC3 and C4-2). The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP and VCaP cells.
Conclusion:
TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells.
Insights
Erastin induces ferroptosis in prostate cancer (PCa) cells by altering gene expression and cell cycle. TMEFF2 shows potential as a ferroptosis target for PCa treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Limited understanding of erastin's mechanism in prostate cancer (PCa).
- Identification of essential ferroptosis-related genes (FRGs) as potential PCa therapeutic targets is needed.
Purpose of the Study:
- To investigate the molecular mechanism of erastin in PCa cells.
- To identify novel ferroptosis-related genes as potential therapeutic targets for PCa.
Main Methods:
- In vitro assays and RNA-sequencing to analyze differentially expressed genes (DEGs) in erastin-treated PCa cells.
- Bioinformatic analyses to identify key pathways and hub genes.
- Gene expression analysis and cell viability assays.
Main Results:
- Erastin inhibited SLC7A11 expression and cell viability, increasing MDA and Fe2+ levels while decreasing GSH and GSSG.
- 295 overlapping DEGs were identified, enriched in DNA replication and cell cycle pathways, leading to G1 phase arrest.
- TMEFF2 was upregulated in PCa tissue, and its knockdown affected SLC7A11 expression and cell viability in androgen-dependent cell lines.
Conclusions:
- TMEFF2 is a potential ferroptosis target for PCa.
- This study elucidates the molecular mechanisms of erastin in PCa, offering insights for targeted therapies.
