Objective. Prostatitis is a common disease of the male genitourinary system, which seriously disturbs the physical and mental health of male patients. It is related to many factors such as living habits, age, and race, but the etiology has not been fully elucidated. This study investigated whether there is a causal relationship between clinical biochemical indicators (i.e., intermediate phenotype) and prostatitis through Mendelian randomization. The subjects of the study were prostatitis patients and related SNPs in the Guangxi Fangchenggang health examination cohort. Methods. According to the requirements of Mendelian randomization (MR), the single nucleotide polymorphisms (SNPs) related to prostatitis patients and 29 common SNPs related to clinical biochemical indicators were analyzed by linkage disequilibrium, and the calculated SNPs were selected. Finally, the related SNPs were analyzed by Mendelian randomization method. Results. 15 biochemical indicators such as complement C4, FOL, CRP, HCY, and estradiol have shared chronic prostatitis SNP sites, and five qualified SNPs were finally screened for complement C4. Finally, complement C4 was obtained by Mendelian randomization method ( P = 0.039 ), which was statistically significant. The other 28 clinical endophenotypes were all negative. Conclusion. The results show that there was a causal relationship between complement C4 and prostatitis, and the more consistent SNP is rs2075799.
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 treatment targets are rarely known. In the current study, in vitro assays were performed to evaluate the ferroptotic levels of PCa cells under erastin treatment. RNA-seq 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, module, transcription factors, and expression levels of DEGs. Erastin inhibited the expression of ferroptosis marker SLC7A11 and cell survivability in both PCa cells. After treatment with erastin, the concentration level of MDA and Fe2+ significantly increased, whereas GSH and GSSG significantly decreased in PCa cells. A total of 295 overlapping DEGs were screened and identified in two cells under erastin exposure and significantly enriched for association with some pathways. The expression levels of four hub FRGs, including TMEFF2, CLU, NRXN3, and UNC5B, were significantly different in PCa and normal tissues. TMEFF2 was the gene co-expressed with SLC7A11 and GPX4. In both PCa cells, the expression levels of SLC7A11 and cell growth were inhibited after the knockdown of TMEFF2. The concentration of Fe2+ significantly increased in two TMEFF2 downregulated cells. In conclusion, FRGs and their correlations with ferroptosis in PCa were identified and validated. Our results showed that these FRGs play a crucial role in PCa, and offered the potential therapeutic target genes for the investigation and treatment of PCa.
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. In the current study, in vitro assays were performed to evaluate the ferroptotic levels of PCa cells under erastin treatment. RNA-sequecing 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, modules, transcription factors, and expression levels of DEGs. Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentration 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 screened and identified in two cells under erastin exposure and significantly enriched for association with several pathways, including DNA replication, steroid hormone biosynthesis, and cell cycle, et al. For four hub FRGs, TMEFF2 in PCa tissue is higher than in normal tissue and the expression levels of CLU, NRXN3, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in LNCaP cells but not in PC3 cells. The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP cells. This study extends our understanding of the molecular mechanism in erastin-affected PCa cells, and provides potential treatment ideas for PCa therapy.
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