RBM25 drives hepatocellular carcinoma progression by regulating oncogenic splicing of MYPT1 and translation of YAP

However, pinpointing the targets and understanding the inherent mechanisms of AS in Hepatocellular Carcinoma (HCC) tumorigenesis remains a complex task. Here, we demonstrate that RNA-binding motif protein 25 (RBM25) is overexpressed in HCC patients, and its elevated expression is associated with worse prognosis.

Functionally, we confirmed that depletion of RBM25 inhibited HCC progression both in vivo and in vitro. Using RNA-seq, we conducted a comprehensive screening and identified numerous AS events affected by RBM25. Particularly, we found that RBM25 regulates the splicing switch of MYPT1 gene, thereby promoting the expression of the oncogenic isoform MYPT1-L. Consistently, MYPT1-L was overexpressed in HCC patients, and a higher level of MYPT1-L was associated with reduced survival rates.