Upregulated and in Osteosarcoma: Association with Poor Prognosis, Immune Cell Infiltration, and Inhibitory Effects of Sphingosine Kinase 1 Inhibitor II/Pilaralisib.

[PURPOSE] and , key RecQ helicases and "genome guardians", maintain genomic stability. Their abnormal function/dysregulated expression is linked to tumorigenesis, but their roles in osteosarcoma (OS) remain unclear.

[PATIENTS AND METHODS] Comprehensive bioinformatic analyses (multiple public databases) assess OS-related expression, gene networks, prognosis, targets, and drugs. Cellular experiments verified the effects of these compounds on 143B cell proliferation, migration, and invasion.

[RESULTS] and were significantly upregulated in OS tissues compared to normal tissues, correlating with a poor prognosis. Among the 153 patients with OS, 9% and 7% had altered and expression, respectively. Abnormal methylation of and may affect OS. , and their altered neighboring genes (ANGs) form interaction networks that regulate tumor metabolism, proliferation, migration, and apoptosis. Their miRNA and kinase targets in OS were also identified. and expression was negatively correlated with OS immune cell infiltration. In addition, anti-PD-1/CTLA-4/PD-L1 therapy, Sphingosine kinase 1 inhibitor II, and pilaralisib inhibited OS cell viability (by downregulating or ) and the proliferation, migration, and invasion of 143B cells. Knockdown of or suppressed the migration and invasion of 143B cells.

[CONCLUSION] and are promising prognostic biomarkers and therapeutic targets for OS.