The alternative splicing events and the function of TLN1 in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC), the most common and aggressive subtype of kidney cancer, exhibits strong metastatic potential. Alternative splicing (AS) represents a critical regulatory layer of gene expression, yet its dysregulation in ccRCC remains insufficiently characterized. ccRCC datasets from GEO were analyzed using DESeq2 for differential gene expression and AS profiling. Gene Ontology enrichment was performed for differentially expressed genes (DEGs) and differentially AS event genes (DASEGs). Findings were compared with TCGA-KIRC to identify shared and Chinese-specific DASEs. An expression regulatory network linking differentially expressed RNA-binding proteins (RBPs) to DASEGs was constructed to screen key AS-regulated genes. Functional roles of the candidate gene TLN1 were validated by molecular and cellular experiments. Analysis of GSE126964 identified 2,295 DEGs and 1,331 DASEs, both enriched in platelet activation and degranulation pathways. Intersecting DEGs and DASEGs yielded 153 key genes. Comparison with TCGA-KIRC revealed 281 Chinese-specific DASEGs, including ALDOA, TLN1, LAMP2, and CD63. The RBP-DASEG network highlighted ALDOA, TLN1, and LAMP2 as potential core regulators associated with platelet pathways. TLN1 was markedly overexpressed in ccRCC tissues and cell lines, and its knockdown significantly reduced proliferation, migration, and colony formation in vitro, supporting a pro-tumorigenic function. This study uncovers platelet-related AS dysregulation in ccRCC and identifies TLN1 as a promising biomarker and therapeutic target, offering new insights into ccRCC pathogenesis and treatment strategies.