Abstract
OBJECTIVE: To explore the genetic alterations, pathobiological functions, and downstream molecular mediators of RBM10 in endometrial cancer (EC) cells. METHODS: Targeted sequencing and The Cancer Genome Atlas (TCGA) dataset analysis were performed. Following knockout (KO) or exogenous overexpression of RBM10 in EC cell lines, the biological functions and underlying mechanism of RBM10 in EC cells were evaluated by Western blot, qRT-PCR, CCK-8, Transwell, RNA-sequencing (RNA-seq), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: RBM10 mutation was present in a subset of ECs. RBM10 KO EC cells showed increased growth, migration, and invasion, compared to parental cells. Conversely, RBM10 overexpression reduced EC cell growth, migration, and invasion. KEGG pathway enrichment analysis showed that the expression of the Hippo-YAP pathway downstream targets was markedly upregulated in RBM10 KO EC cells. Mechanistically, RBM10 suppressed Yes Kinase-associated Protein (YAP) activity by promoting YAP phosphorylation. CONCLUSION: RBM10 acts as tumor suppressor in EC by modulating the Hippo-YAP signaling pathway.