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

Abstract:

: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.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Zhan YT,Li L,Zeng TT,Zhou NN,Guan XY,Li Y

doi

10.18632/aging.202164

subject

Has Abstract

pub_date

2020-12-03 00:00:00

pages

537-554

issue

1

issn

1945-4589

pii

202164

journal_volume

13

pub_type

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