Affiliation:
1. Central South University
2. Kunming Medical University
Abstract
Abstract
Background: SNRPB2, a spliceosome component, is well known to participate in the pre-splicing of mRNA and plays a crucial role in the progression of several cancers. However, its precise effect on HCC remains unexplored.
Methods: Bioinformatics analysis was carried out using TCGA, GTEx, GEO, HPA, CPTAC, Kaplan-Meier plotter, RNAactDrug, and R Studio.The level of SNRPB2 expression in HCC was validated via RT-qPCR, western blot, and IHC. Functional experiments, including CCK8, transwell, and colony formation assays, as well as nude mouse xenograft model, were employed for the purpose of in vitro and in vivo validation. IHC, CCK8, colony formation assays, and measurements of GSH, lipid ROS, and ferrous iron were performed to evaluate the impact of SNRPB2 on the ferroptosis of HCC cells. Databases including miRDB, miRWalk, Targetscan, miRabel, CancerMIRNome, and ENCORI, correlation analysis, RT-qPCR, and luciferase reporter assays were employed to identify the ceRNA regulatory axis of SNRPB2. Sorafenib resistant HepG2 cell line was developed to examine the effect of SNRPB2 on sorafenib resistance.
Results: Here, we demonstrate that high level of SNRPB2 is significantly associated with poor outcomes in HCC patients. Additionally, inhibiting SNRPB2 may accelerate ferroptosis, thereby suppressing HCC tumor development. Moreover, SNRPB2 is regulated by the SNHG4/miR-204-5p axis, and increased SNHG4 could reverse the effect of SNRPB2 knockdown. Finally, SNRPB2 deficiency increases the sorafenib sensitivity of HCC cells.
Conclusion: Conclusively, our study uncovers the previously unknown role of SNRPB2 in HCC, reveals the related ceRNA regulatory axis of SNRPB2, and identifies a novel ferroptosis regulating protein, suggesting SNRPB2 appears to be a promising target for HCC therapy.
Publisher
Research Square Platform LLC
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