RNA Binding protein KPNA2 promotes the progress of gastric cancer by regulating alternative splicing of related genes [RNA-seq]

RNA binding proteins (RBPs) took a critical part in genome regulation. kpna2, as an essential member of the RBP family, was found to be highly expressed and associated with lymph node metastasis in gastric cancer (GC). Transcriptional sequencing data were used to find that KPNA2 primarily regulated alternative 5' splice site (A5SS), alternative 3'splice site (A3SS), exon skipping (ES) and cassette exon. Vitally, KPNA2 was involved in the transcriptional regulation of cancer-related genes. Therefore, we screened potential targets in AGS cells with differential expression and alternative splicing (AS) levels regulated by KPNA2, further identifying that KPNA2 was engaged in biological processes concerning immune response, cell proliferation and apoptosis in GC through transcriptional regulation. Besides, the binding sites of KPNA2 to spliceosomes were identified using improved RNA immunoprecipitation sequencing techniques, and KPNA2 was preferentially bound to the intron region. Notably, KPNA2 regulated the A3SS AS mode of WDR62, which may increase the malignancy of GC. Finally, we also discovered that AS of immune-related molecules can be regulated by KPNA2. Overall, for the first time, our results demonstrated that KPNA2 served as an oncogenic splicing factor in GC regulating AS and differential expression of GC-related genes and may represent a potential target for GC therap