Bioinformatics and experimental approaches identify NME8 as a promoter of the metastasis of renal cell carcinoma by activating the JAK/STAT signaling pathway.

Renal cell carcinoma (RCC) presents treatment challenges in advanced stages owing to its metastatic potential. This study explored the role of NME8, a nucleotide metabolism-related protein, in the metastasis and prognosis of RCC. Analysis of the GSE66272 dataset and of The Cancer Genome Atlas (TCGA) specimens revealed that NME8 is overexpressed in renal cancer and is correlated with poor patient outcomes, as determined by Cox regression. Functional assessments, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses and immune infiltration studies, were conducted. In vitro experiments involving the creation of stable NME8-knockdown cell lines revealed that NME8 knockdown significantly reduced renal cancer cell proliferation, migration, and invasion while increasing apoptosis. Immunoblotting indicated that NME8 was associated with epithelial-mesenchymal transition (EMT) proteins such as E-cadherin, vimentin, and Twist. Furthermore, exposure to the Janus kinase (JAK) inhibitor ruxolitinib and the signal transducer and activator of transcription (STAT)3 inhibitor stattic demonstrated that NME8 promoted RCC metastasis by activating the JAK/STAT signaling pathway. Elevated NME8 levels were linked to immune cell infiltration. In conclusion, our findings suggest that NME8 contributes to RCC metastasis by promoting JAK/STAT-mediated EMT and modulating the tumor immune microenvironment. While elevated NME8 expression correlates with poor prognosis in public cohorts, its utility as a clinical prognostic biomarker requires further validation in independent patient populations.