Cytoglobin overexpression-dependent transcriptomic changes in A375 melanoma cells
Cytoglobin (CYGB) is a member of the oxygen-binding globin superfamily. In this study, we comprehensively explored the CYGB-dependent transcriptome in A375 melanoma cells overexpressing CYGB. Our findings reveal that CYGB overexpression positively enriches cancer-associated pathways, including the mTORC1 and AKT/mTOR signaling pathways, which are frequently overactivated in tumors. Moreover, several cancer-associated pathways, such as epithelial-mesenchymal transition (EMT) mediated by CSPG4, were downregulated upon CYGB overexpression. Intriguingly, our results indicate that CYGB overexpression leads to a reduction in the inflammatory state of melanoma cells. This anti-inflammatory potential is exemplified by the downregulation of key inflammasome-associated genes, including NLRP1, CASP1, and CD74, which play pivotal roles in cytokine regulation and inflammasome activation. Consistent with established globin functions, CYGB appears to play a crucial role in redox homeostasis. Furthermore, our study highlights CYGB's involvement in DNA repair mechanisms and its regulation of NOX4, reinforcing its versatility in safeguarding genomic integrity. Collectively, our data illuminate the diverse functions of CYGB in melanoma cells, pointing to its roles in cellular protection against oxidative stress, inflammation, and cancer-associated pathways. These findings pave the way for further research into the physiological role of CYGB and its potential as a therapeutic target in melanoma. Overall design: Differential gene expression analysis of CYGB overexpressing A375 melanoma cells compared to A375 wildtype melanoma cells