SF3A3 regulates the proliferation and migration capabilities of hepatocellular carcinoma cells via the Notch signaling pathway

This study aims to investigate the expression, biological function, and molecular mechanism of the splicing factor SF3A3 in hepatocellular carcinoma (HCC). Analysis of the TCGA-LIHC cohort revealed that SF3A3 is significantly upregulated in HCC tissues and its high expression correlates with poor overall survival. We established SF3A3 knockdown and overexpression models in HepG2 and Huh7 cells. Functional assays (CCK-8, colony formation, EdU, wound healing, flow cytometry for cell cycle and apoptosis) demonstrated that SF3A3 overexpression promotes HCC cell proliferation and migration, whereas knockdown exerts opposite effects. To explore the underlying mechanism, we performed transcriptome sequencing (RNA-seq) on SF3A3-depleted HCC cells. Combined with bioinformatic analysis and validation using the GEO dataset GSE287381, we identified the Notch signaling pathway as a key target of SF3A3. Western blotting confirmed that SF3A3 knockdown reduces Notch1 and HES1 protein levels, while overexpression increases them. Collectively, our findings indicate that SF3A3 promotes HCC cell proliferation and migration by activating the Notch signaling pathway, providing a rationale for targeting the SF3A3-Notch axis in HCC therapy.