Identification of the hub gene BUB1B in hepatocellular carcinoma via bioinformatic analysis and in vitro experiments

Jie Fu; Xiao Zhang; Likun Yan; Yaoli Shao; Xinxu Liu; Yuan Chu; Ge Xu; Xundi Xu

doi:10.7717/peerj.10943

Identification of the hub gene BUB1B in hepatocellular carcinoma via bioinformatic analysis and in vitro experiments

PeerJ. 2021 Feb 23:9:e10943. doi: 10.7717/peerj.10943. eCollection 2021.

Authors

Jie Fu^{1

2}, Xiao Zhang^{1

2}, Likun Yan^{1

2}, Yaoli Shao^{1

2}, Xinxu Liu^{1

2}, Yuan Chu^{1

2}, Ge Xu^{1

2}, Xundi Xu^{1

2}

Affiliations

¹ Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related deaths in the world. Although the treatment of HCC has made great progress in recent years, the therapeutic effects on HCC are still unsatisfactory due to difficulty in early diagnosis, chemoresistance and high recurrence rate post-surgery.

Methods: In this study, we identified differentially expressed genes (DEGs) based on four Gene Expression Omnibus (GEO) datasets (GSE45267, GSE98383, GSE101685 and GSE112790) between HCC and normal hepatic tissues. A protein-protein interaction (PPI) network was established to identify the central nodes associated with HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the central nodes were conducted to find the hub genes. The expression levels of the hub genes were validated based on the ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Additionally, the genetic alterations of the hub genes were evaluated by cBioPortal. The role of the hub genes on the overall survival (OS) and relapse survival (RFS) of HCC patients was evaluated by Kaplan-Meier plotter. At last, the mechanistic role of the hub genes was illustrated by in vitro experiments.

Results: We found the following seven hub genes: BUB1B, CCNB1, CCNB2, CDC20, CDK1, MAD2L1 and RRM2 using integrated bioinformatics analysis. All of the hub genes were significantly upregulated in HCC tissues. And the seven hub genes were associated with the OS and RFS of HCC patients. Finally, in vitro experiments indicated that BUB1B played roles in HCC cell proliferation, migration, invasion, apoptosis and cell cycle by partially affecting mitochondrial functions.

Conclusions: In summary, we identified seven hub genes that were associated with the expression and prognosis of HCC. The mechanistic oncogenic role of BUB1B in HCC was first illustrated. BUB1B might play an important role in HCC and could be potential therapeutic targets for HCC.

Keywords: BUB1B; Bioinformatic analysis; Hepatocellular carcinoma; Hub genes; In vitro.

Grants and funding

This work was supported by the National Natural Science Foundation of China, grant 81670111. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.