LSM5 is associated with malignant phenotypes in osteosarcoma: an integrative pan-cancer analysis

LSM5 is a member of the Sm-like (LSM) protein family and plays a critical role in pre-mRNA splicing. However, its expression landscape across cancers and its biological functions in osteosarcoma remain poorly understood. This study aimed to characterise LSM5 expression across cancers, examine its associations with cell-cycle state, clinical outcome and genomic instability, and assess its associations with osteosarcoma cell proliferation and migration. LSM5 expression, exploratory tumor-versus-normal discrimination, prognostic significance, and associations with genomic instability were analysed across cancers using TCGA and GEO databases. Single-cell transcriptomic data from TISCH2 were integrated to assess LSM5 expression patterns and cell-type distribution. In osteosarcoma cells, wound healing, Transwell migration and invasion, EdU incorporation and tumoursphere formation assays were performed, and flow cytometry was used to detect cell-cycle distribution. LSM5 was broadly over-expressed across cancer types and was positively correlated with tumor status and genomic instability. Single-cell analysis revealed a cell cycle-dependent expression pattern of LSM5. In osteosarcoma, high LSM5 expression was associated with shorter survival in two public cohorts. LSM5 knockdown was associated with reduced cell migration, invasion, EdU incorporation and tumoursphere formation, and with G0/G1 phase arrest, accompanied by upregulation of p53 and p21 and downregulation of Cyclin D1; LSM5 overexpression showed the opposite pattern. LSM5 expression was associated with the G1/S transition and with the abundance of p53, p21 and Cyclin D1 in osteosarcoma cells. These findings identify LSM5 as a candidate prognostic marker in osteosarcoma that warrants further investigation.