regulates cell proliferation, migration, apoptosis and ferroptosis in gastric cancer.

BACKGROUND

Gastric cancer (GC) has a high prevalence and mortality overall. is associated with abnormal centrosome amplification, DNA damage and increased apoptosis. To date, little is known about the function and mechanism of in GC.

AIM

To explore the cellular processes associated with GC will help to elucidate the mechanism of the occurrence and development of GC and discover potential therapeutic targets.

METHODS

The detection of expression at mRNA and protein levels was done by real-time quantitative polymerase chain reaction and western blotting. The function of was verified by loss-of-function experiments in AGS cells. The genes co-expressed with were searched from the stomach adenocarcinomas (STAD) data in The Cancer Genome Atlas database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes co-expressed with to further identify the pathways involved in . Rescue experiments using ferroptosis inhibitor ferrostatin-1 and chemotherapeutic sensitivity assays with cisplatin were also performed.

RESULTS

Significant up-regulation of was observed in GC cell lines AGS and MGC-803. Inhibition of induced cell apoptosis and decreased cell proliferation, cycle progression, migration in AGS cells. There were 264 genes co-expressed with in STAD cohort ( > 0.4, < 0.001). KEGG enrichment analysis showed that might be associated with the cell cycle, Fanconi anemia pathway, homologous recombination, oocyte meiosis and cellular senescence in GC. Furthermore, , , , cyclin-dependent kinase (CDK) 1, CDK2 and polo-like kinase 1 protein levels were lower in -knockdown AGS cells, manifesting that was associated with the cell cycle pathway in AGS cells. Downregulation of decreased adenosine triphosphate content and elevated reactive oxygen species in AGS cells, suggesting that silencing led to mitochondrial dysfunction in AGS cells. In addition, silencing caused an overt decrease in and protein levels and a significant elevation in protein levels, implying that silencing promoted AGS cell ferroptosis. Treatment with ferrostatin-1 rescued cell viability loss induced by knockdown, confirming ferroptosis as a key death mechanism. Additionally, -deficient AGS cells showed enhanced sensitivity to cisplatin, with a significantly reduced half-maximal inhibitory concentration compared to control cells.

CONCLUSION

promotes GC cell proliferation and migration while suppressing apoptosis and ferroptosis. Targeting not only disrupts mitochondrial function and cell cycle progression but also sensitizes GC cells to ferroptosis and chemotherapy. These findings highlight as a potential therapeutic target for enhancing treatment efficacy in gastric cancer.