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

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.

Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments

“…Total RNA was extracted from PDAC cells using RNAiso Plus Reagent (Takara, Japan). qRT-PCR and data analysis were performed as previously described (Fu et al, 2021). Specifically, GAPDH was used as an internal control.…”

“…Cell cycle were measured by flow cytometry. Flow cytometry was performed as previously described (Fu et al, 2021). Briefly, PDAC cells after treatments were fixed in 70% ethanol at −20 C overnight.…”

Altered Cathepsin B Expression as a Diagnostic Marker of Skeletal Muscle Insulin Resistance in Type 2 Diabetes

“…The development of bioinformatics analysis tools combined with in vitro experiments has facilitated the discovery of novel genes and pathways in the progression of human diseases from multiple levels along with the exploration of biomarkers associated with the disease survival, prognosis, diagnosis and treatment. − Based on the GEO database and in vitro cell experiments, the current investigation revealed that CTSB could be used as a diagnostic marker for the IR of skeletal muscle in T2DM, and that overexpression of CTSB was able to inhibit palmitate-induced IR in human SkMCs.…”

Immune-related lincRNA pairs predict prognosis and therapeutic response in hepatocellular carcinoma

“…For instance, a recent study has demonstrated that CDCA8 promotes HCC growth and stemness through the AKT/β-catenin signaling 53 . BUB1B exerts an oncogenic effect in HCC cell proliferation, migration, and invasion partially by affecting mitochondrial function 54 . CDC20 could enhance cell proliferation and is associated with the development and progression of HCC 55 .…”