Study on the Key Role of Oncofetal snrpe in the Tumorigenesis and Progression of Hepatocellular Carcinoma

Research Background and Purpose

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. However, due to the lack of understanding of key molecular events in tumors, effective therapeutic targets for HCC remain quite limited. This study focuses on the significant changes in spliceosome-related genes in HCC, exploring the potential of fetal proteins associated with spliceosomes during embryonic liver development and HCC as therapeutic targets for tumors.

Research Source

This study was jointly completed by Wu Qipeng, Liao Ruyan, Miao Chunmeng, Hasnat Muhammad, Li Le, Sun Lixin, Wang Xinru, Yuan Ziqiao, Jiang Zhenzhou, Zhang Luyong, and Yu Qinwei. The institutions involved include China Pharmaceutical University, Guangzhou Customs Technology Center, University of Veterinary and Animal Sciences Lahore, Zhengzhou University, Guangdong Pharmaceutical University, among others. The research findings were published in the British Journal of Cancer in 2024, with the article DOI being 10.1038/s41416-024-02689-5.

Research Methods

Firstly, the study used bioinformatics methods to analyze differentially expressed spliceosome genes in embryonic liver and HCC. By analyzing the expression of small nuclear ribonucleoprotein polypeptide E (snrpe) in embryonic liver, adult liver, and HCC tissues, and employing various in vitro and in vivo experiments to evaluate the role of snrpe in HCC. The study found that snrpe promotes tumorigenesis by regulating the splicing variant expression of fetal growth factor receptor 4 (fgfr4). High-throughput RNA sequencing identified splicing variants regulated by snrpe.

Main Findings

The study found that snrpe is a key embryonic splicing factor significantly associated with poor prognosis in HCC. The research identified the reactivation of snrpe expression by the SOX2 factor. Effective silencing of the snrpe gene could completely prevent the occurrence and progression of HCC tumors. Mechanistic analysis showed that silencing the snrpe gene triggered nonsense-mediated mRNA decay, reducing the expression of fgfr4 mRNA. Under conditions of fgfr4 gene silencing, partial inhibition of snrpe-induced HCC cell malignant progression was observed.

Research Conclusion and Significance

The study results highlight the potential of snrpe as a therapeutic target for HCC and reveal the complex relationship between embryonic splicing factors, splicing events, and cancer occurrence. This provides a scientific basis for developing new strategies to target HCC treatment.

Research Highlights

The discovery of snrpe’s critical role as a new fetal splicing factor in HCC has important implications. The study not only emphasizes the importance of addressing the problem, i.e., the connection between embryonic splicing factors and cancer occurrence, but also showcases innovative research methods, particularly the specificity of the research target snrpe.