Oncofetal SNRPE promotes HCC tumorigenesis by regulating FGFR4 expression through alternative splicing

Abstract

Abstract Understanding the roles of spliceosome and splicing events during tumorigenesis opens new avenues for targeted therapies. Here, we identified that small nuclear ribonucleoprotein polypeptide E (SNPRE) is an oncofetal splicing factor, which had a link in the poor prognosis of hepatocellular carcinoma (HCC), and was reactivated by SOX2. SNRPE knockdown effectively abolished HCC tumorigenesis and progression. Transcriptome analysis and RT-PCR results revealed that SNRPE knockdown induced intron retention (intron 4) in the fibroblast growth factor receptor 4 (FGFR4) transcript. Mechanistically, SNRPE knockdown reduced FGFR4 mRNA expression by activating nonsense-mediated RNA decay. FGFR4 knockdown partially blocked the SNRPE-induced malignant progression of HCC cells. Our findings discovered SNRPE as a novel oncofetal splicing factor and elucidated the relationship between oncofetal splicing factors, splicing events and carcinogenesis. Therefore, SNRPE is a potential target for HCC treatment.