由于对关键分子事件认识不足，肝细胞癌（HCC）缺乏有效的治疗靶点。剪接体相关基因在 HCC 中发生显着改变。癌胎蛋白是理想的肿瘤治疗靶点。筛选胚胎肝脏发育和肝癌中差异表达的剪接体相关癌胚蛋白，有助于发现肝癌的有效治疗靶点。通过生物信息学分析，对胎儿肝脏和肝癌中差异表达的剪接体基因进行分析。在胎儿肝脏、成人肝脏和 HCC 组织中检测到小核核糖核蛋白多肽 E (SNRPE) 表达。 SNRPE 在 HCC 中的作用在体外和体内进行了多次测定。 SNRPE 调节的选择性剪接已被 RNA-Seq 识别，并通过多种测定得到证实。我们在此确定 SNRPE 是一个重要的癌胚剪接因子，与 HCC 的不良预后显着相关。 SOX2 被确定为 SNRPE 重新激活的激活剂。 SNRPE 的有效敲低导致 HCC 肿瘤发生和进展的完全停止。从机制上讲，SNRPE 敲低通过触发无义介导的 RNA 衰减来减少 FGFR4 mRNA 表达。 FGFR4 敲低后观察到 SNRPE 诱导的 HCC 细胞恶性进展得到部分抑制。我们的研究结果强调了 SNRPE 作为一种新型癌胚剪接因子，并揭示了癌胚剪接因子、剪接事件和癌发生之间的复杂关系。因此，SNRPE 成为 HCC 治疗的潜在治疗靶点。癌胎儿 SNRPE 模型通过调节 FGFR4 前 mRNA 的 AS 促进 HCC 肿瘤发生。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Due to insufficient knowledge about key molecular events, Hepatocellular carcinoma (HCC) lacks effective treatment targets. Spliceosome-related genes were significantly altered in HCC. Oncofetal proteins are ideal tumor therapeutic targets. Screening of differentially expressed Spliceosome-related oncofetal protein in embryonic liver development and HCC helps discover effective therapeutic targets for HCC.Differentially expressed spliceosome genes were analysis in fetal liver and HCC through bioinformatics analysis. Small nuclear ribonucleoprotein polypeptide E (SNRPE) expression was detected in fetal liver, adult liver and HCC tissues. The role of SNRPE in HCC was performed multiple assays in vitro and in vivo. SNRPE-regulated alternative splicing was recognized by RNA-Seq and confirmed by multiple assays.We herein identified SNRPE as a crucial oncofetal splicing factor, significantly associated with the adverse prognosis of HCC. SOX2 was identified as the activator for SNRPE reactivation. Efficient knockdown of SNRPE resulted in the complete cessation of HCC tumorigenesis and progression. Mechanistically, SNRPE knockdown reduced FGFR4 mRNA expression by triggering nonsense-mediated RNA decay. A partial inhibition of SNRPE-induced malignant progression of HCC cells was observed upon FGFR4 knockdown.Our findings highlight SNRPE as a novel oncofetal splicing factor and shed light on the intricate relationship between oncofetal splicing factors, splicing events, and carcinogenesis. Consequently, SNRPE emerges as a potential therapeutic target for HCC treatment. Model of oncofetal SNRPE promotes HCC tumorigenesis by regulating the AS of FGFR4 pre-mRNA.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.