Research Paper Volume 16, Issue 1 pp 348—366
SNRPB promotes the progression of hepatocellular carcinoma via regulating cell cycle, oxidative stress, and ferroptosis
- 1 Department of Experimental Teaching Center, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin 541199, Guangxi, China
- 2 Key Laboratory of Biochemistry and Molecular Biology, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin 541199, Guangxi, China
- 3 Department of Biomedical Engineering, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin 541199, Guangxi, China
- 4 Department of Biochemistry, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin 541199, Guangxi, China
Received: August 22, 2023 Accepted: November 21, 2023 Published: January 5, 2024
https://doi.org/10.18632/aging.205371How to Cite
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) have been linked to multiple human cancers. However, the mechanism of SNRPB in hepatocellular carcinoma (HCC) and whether SNRPB has a synergistic effect with sorafenib in the treatment of HCC remain unclear. In this study, bioinformatic analysis found that SNRPB was an independent prognostic factor for HCC that exerted a critical effect on the progression of HCC. SNRPB was linked with immune checkpoints, cell cycle, oxidative stress and ferroptosis in HCC. Single cell sequencing analysis found that HCC cell subset with high expression of SNRPB, accounted for a higher proportion in HCC cells with higher stages, had higher expression levels of the genes which promote cell cycle, inhibit oxidative stress and ferroptosis, and had higher cell cycle score, lower oxidative stress score and ferroptosis score. Single-sample gene set enrichment analysis (ssGSEA) analysis found that 17 oxidative stress pathways and 68 oxidative stress-ferroptosis related genes were significantly correlated with SNRPB risk scores. SNRPB knockdown induced cell cycle G2/M arrest and restrained cell proliferation, while downregulated the expression of CDK1, CDK4, and CyclinB1. The combined treatment (SNRPB knockdown+sorafenib) significantly inhibited tumor growth. In addition, the expression of SLC7A11, which is closely-related to ferroptosis, decreased significantly in vitro and in vivo. Therefore, SNRPB may promote HCC progression by regulating immune checkpoints, cell cycle, oxidative stress and ferroptosis, while its downregulation inhibits cell proliferation, which enhances the therapeutic effect of sorafenib, providing a novel basis for the development of HCC therapies.
Abbreviations
AUC: Area Under Curve; Act: CD8 activated CD8+ T; CDKs: cyclin-dependent kinases; DEGs: identify differentially expressed genes; GSEA: Gene Set Enrichment Analysis; HCC: hepatocellular carcinoma; HE: Hematoxylin-eosin staining; IHC: Immunohistochemistry; ICGC: International Cancer Genome Consortium; KEGG: Kyoto Encyclopedia of Genes and Genomes; LIHC: liver hepatocellular carcinoma; NK: Natural killer; pDC: plasmacytoid dendritic cells; PBS: phosphate-buffered saline; ROC: receiver operating characteristic; ROS: reactive oxygen species; ssGSEA: Single sample gene set enrichment analysis; snRNP: spliceosomal U1, U2, U4, and U5; SNRPB: Small Nuclear Ribonucleoprotein Polypeptides B and B1; TCGA: The Cancer Genome Atlas; Tcm: CD8 central memory CD8+ T; Tem: CD8 effector memory CD8+ T; Tgd: gammadelta T; Th1: T helper 1; t-SNE: t-distributes stochastic neighbor embedding.