Research Paper Volume 13, Issue 1 pp 537—554
SNRPB-mediated RNA splicing drives tumor cell proliferation and stemness in hepatocellular carcinoma
- 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- 2 Department of Clinical Oncology, The University of Hong Kong, Hong Kong 852, P. R. China
Received: May 18, 2020 Accepted: September 28, 2020 Published: December 3, 2020https://doi.org/10.18632/aging.202164
How to Cite
Copyright: © 2020 Zhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
GEO: Gene Expression Omnibus; GO: Gene Ontology; HCC: hepatocellular carcinoma; IHC: immunehisto chemical; PBS: phosphate buffered saline; qRT-PCR: quantitative reverse transcription PCR; RT-PCR: reverse transcription PCR; SAPs: spliceosome-associated proteins; shRNA: short hairpin RNA; snRNPs: small nuclear ribonucleoproteins; SNRPB: Small Nuclear Ribonucle oprotein Polypeptides B and B1; TBST: Tris-buffered saline/Tween 20; TCGA: The Cancer Genome Atlas.