目的 探讨SNRPB（small nuclear ribonucleoprotein polypeptides B and B1）在肝细胞癌（hepatocellular carcinoma,HCC）中的促癌作用及其分子机制。方法 通过多组学数据库分析SNRPB在HCC中的表达及临床意义;利用Western blot、Transwell实验检测SNRPB对HCC细胞迁移和侵袭能力的影响;采用双荧光素酶报告实验、免疫共沉淀实验及泛素化实验探究SNRPB调控Hippo信号通路的分子机制。结果 SNRPB在HCC组织及细胞系中高表达,且与患者不良预后显著相关。功能实验表明,SNRPB促进HCC细胞迁移和侵袭。机制研究发现,SNRPB通过与YAP蛋白结合,抑制其泛素化降解,从而稳定YAP蛋白并增强下游靶基因CTGF的转录活性。此外,YAP可反馈调控SNRPB表达,形成SNRPB-YAP正反馈环路。结论 SNRPB通过调控Hippo信号通路促进HCC进展,为HCC治疗提供了新的潜在靶点。
Abstract
Objective To investigate the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in hepatocellular carcinoma (HCC) and its underlying molecular mechanisms. Methods Multi-omics databases were utilized to analyze the expression and clinical significance of SNRPB in HCC. The effects of SNRPB on HCC cell migration and invasion were evaluated using Western blot and Transwell assay. The molecular mechanisms of SNRPB in regulating the Hippo signaling pathway were investigated through dual-luciferase reporter assay, co-immunoprecipitation (Co-IP), and ubiquitination assays. Results SNRPB was highly expressed in HCC tissues and cell lines, and its expression was significantly associated with poor prognosis in patients. Functional experiments demonstrated that SNRPB promoted HCC cell migration and invasion. Mechanistic studies revealed that SNRPB interacted with YAP protein, inhibited its ubiquitination-mediated degradation, and thereby stabilized YAP protein, enhancing the transcriptional activity of the downstream target gene CTGF. Furthermore, YAP positively regulated SNRPB expression, forming a SNRPB-YAP positive feedback loop. Conclusion SNRPB promotes HCC progression by modulating the Hippo signaling pathway, offering a novel potential therapeutic target for HCC treatment.
关键词
SNRPB /
RNA结合蛋白 /
Hippo信号通路 /
肝细胞癌
Key words
SNRPB /
RNA-binding proteins /
Hippo signaling pathway /
hepatocellular carcinoma
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基金
湖南省自然科学基金“RNA结合蛋白对Hippo信号通路的调控作用与机制研究”（2023JJ20029）; 湖南省卫生与健康委员会重点项目“RBP调控Hippo信号通路与肝癌发生的机制研究”（C202302088169）
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