期刊
AGING-US
卷 13, 期 1, 页码 537-554出版社
IMPACT JOURNALS LLC
关键词
hepatocellular carcinoma; RNA splicing; cancer stem cell; glycolysis; SNRPB
资金
- NSFC [82072604, 82072738]
- National Key R&D Program of China [2017YFC130 9000]
- China National Key Sci-Tech Special Project of Infectious Diseases [2018ZX10723204-006-005]
- Open Funds of State Key Laboratory of Oncology in South China [HN2019-06]
- Guangdong Basic and Applied Basic Research Foundation, China [2019A1515110660]
- Hong Kong Research Grant Council Collaborative Research Funds [C7065-18GF, C7026-18GF]
- Shenzhen Peacock team Project [KQDT2015033117210153]
- Hong Kong Research Grant Council General Research Fund [17143716]
The upregulation of SNRPB in HCC is associated with tumor malignancy and patient survival. Functional studies indicate that SNRPB promotes HCC cell proliferation and stemness maintenance, while also inducing metabolic reprogramming in HCC cells. In addition, SNRPB facilitates the formation of specific splice variants that activate pathways contributing to HCC progression.
Hepatocellular carcinoma (HCC) is one of the leading malignant diseases worldwide, but therapeutic targets for HCC are lacking. Here, we characterized a significant upregulation of Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) in HCC via qRT-PCR, western blotting, tissue microarray and public database analyses. Increased SNRPB expression was positively associated with adjacent organ invasion, tumor size, serum AFP level and poor HCC patient survival. Next, we transfected SNRPB into HCC cells to construct SNRPB-overexpressing cell lines, and short hairpin RNA targeting SNRPB was used to silence SNRPB in HCC cells. Functional studies showed that SNRPB overexpression could promote HCC cell malignant proliferation and stemness maintenance. Inversely, SNRPB knockdown in HCC cells caused inverse effects. Importantly, analysis of alternative splicing by RNA sequencing revealed that SNRPB promoted the formation of AKT3-204 and LDHA-220 splice variants, which activated the Akt pathway and aerobic glycolysis in HCC cells. In conclusion, SNRPB could serve as a prognostic predictor for patients with HCC, and it promotes HCC progression by inducing metabolic reprogramming.
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