SNRPB-mediated RNA splicing drives tumor cell proliferation and stemness in hepatocellular carcinoma

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 a...

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Published in:Aging (Albany, NY.) NY.), 2021-01, Vol.13 (1), p.537-554
Main Authors: Zhan, Yu-Ting, Li, Lei, Zeng, Ting-Ting, Zhou, Ning-Ning, Guan, Xin-Yuan, Li, Yan
Format: Article
Language:English
Subjects:
AC133 Antigen - metabolism
alpha-Fetoproteins - metabolism
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Proliferation - genetics
Epithelial Cell Adhesion Molecule - metabolism
Female
Gene Knock-In Techniques
Gene Knockdown Techniques
Humans
Kaplan-Meier Estimate
Keratin-19 - metabolism
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Male
Middle Aged
Neoplasm Invasiveness
Neoplastic Stem Cells - metabolism
Research Paper
RNA Splicing - genetics
snRNP Core Proteins - genetics
Survival Rate
Tumor Burden
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.202164