Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis

Mi, Ningning; Cao, Jie; Zhang, Jinduo; Fu, Wenkang; Huang, Chongfei; Gao, Long; Yue, Ping; Bai, Bing; Lin, Yanyan; Meng, Wenbo; Li, Xun

doi:10.3892/ol.2020.11752

Cited by 9 publications

(6 citation statements)

References 60 publications

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“…Next-generation sequencing (NGS) of the complete RNA transcriptome (RNA-seq) offers a novel approach to systematically characterize the underlying molecular mechanism of diseases. [39][40][41][42] In OR-6 cells treated with SOF 1uM for 24 hours, NGS study was performed and many genes were upregulated by SOF in OR-6 cells. Top-ranked genes were selected for further investigation (Table S1).…”

Section: Sof-upregulated Genes Were Associated With Cancer Developmenmentioning

confidence: 99%

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Tsai

Cheng

Pei-feng

et al. 2020

Preprint

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Background: Direct-acting antivirals (DAAs) have achieved a sustained virological response (SVR) rate of 95-99% in treating HCV. Several studies suggested that treatment with sofosbuvir (SOF) containing DAAs may be associated with increased risk of developing HCC. The aim of this study is to investigate the potential mechanisms of SOF on the development of HCC.Methods: This study used OR-6 (harboring full-length genotype 1b HCV) and Huh 7.5.1 cells to examine the effects of SOF on cell proliferation and migration in HCC cells. SOF-upregulated genes in OR-6 cells were inspected using next generation sequencing (NGS) and the clinical significance of these candidate genes was analyzed using The Cancer Genome Atlas (TCGA) database. siRNA-mediated knockdown of candidate genes and their influence on cell proliferation and migration were also examined.Results: SOF increased cell proliferation and cell migration in OR-6 and Huh7.5.1 cells in both two- and three-dimensional culture models. NGS identified several genes that were significantly upregulated by SOF in OR-6 cells. Among these genes, PHOSPHO2, KLHL23, TRIM39, TSNAX-DISC1 and RPP21 expression were significantly elevated in the tumor part compared with the non-tumor part of HCC in the TCGA database. PHOSPHO2 and RPP21 were found to be associated with overall survival of HCC patients in the TCGA database. Moreover, knockdown of PHOSPHO2-KLHL23, TSNAX-DISC1, TRIM39 and RPP21 ameliorated cell proliferation and migration increased by SOF in OR-6 and Huh 7.5.1 cells. Conclusion: SOF upregulated several genes that were associated with increased cell proliferation and migration and the development of HCC.

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Section: Sof-upregulated Genes Were Associated With Cancer Developmenmentioning

confidence: 99%

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Tsai

Cheng

Pei-feng

et al. 2020

Preprint

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“…Deng et al found that PLK1 inhibition induces mitotic arrest at G2/M phase, leading to HCC cell apoptosis (25). Numerous findings based on bioinformatics confirmed that CDC20 might have a critical regulatory role in the occurrence and progression of HCC (26)(27)(28). Moreover, increased CDC20 was linked to poor prognosis of individuals with HCC (29,30).…”

Section: Discussionmentioning

confidence: 99%

Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma

Wang¹,

Yu²,

Zhang³

et al. 2021

Transl Cancer Res TCR

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Background The high degree of heterogeneity of hepatocellular carcinoma (HCC) imposes a significant challenge to predict the prognosis. Currently, increasing evidence has indicated that cell cycle-linked genes are strongly linked to occurrence and progress of HCC. Herein, we purposed to create a prediction model on the basis of cell cycle-linked genes. Methods The transcriptome along with clinicopathological data abstracted from The Cancer Genome Atlas (TCGA) were used as a training cohort. Lasso regression analysis was employed to create a prediction model in TCGA cohort. The data of samples obtained from the International Cancer Genome Consortium (ICGC) data resource were applied in the verification of the model. A series of bioinformatics analyzed the relationship of the risk signature with overall survival (OS), biological function, and clinicopathological features. Results Six cell cycle-linked genes ( PLK1, CDC20, HSP90AA1, CHEK1, HDAC1 , and NDC80 ) were chosen to create the prognostic model, demonstrating a good prognostic capacity. Further analyses indicated that the model could independently assess the OS of HCC patients. A single-sample gene set enrichment analysis (ssGSEA) indicated that the risk signature was remarkably linked to immune status. Additionally, there was a remarkable association of the risk signature with TP53 mutation frequency, as well as immune checkpoint molecule expression levels. Conclusions We created a prediction model using six cell cycle-linked genes to predict HCC prognosis. The six genes are expected to be novel markers for HCC diagnosis, as well as treatment.

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“…A previous study indicated that CDK1 and BUB1B were mainly involved in cell cycle regulation and cell movement ( 37 ). CCNB1 and CDC20 were identified as crucial genes associated with the pathogenesis and prognosis of pancreatic adenocarcinoma ( 38 ) and hepatocellular carcinoma ( 39 , 40 ). CCNB1 and CDC20 were indicated to be associated with cell cycle and cell proliferation and thus have an important role in tumor progression ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and experimental validation of differentially expressed genes in mouse articular chondrocytes treated with IL‑1β using microarray data

Fan

Peng

et al. 2021

Exp Ther Med

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Osteoarthritis (OA) is the most prevalent chronic degenerative disease that affects the health of the elderly. The present study aimed to identify significant genes involved in OA via bioinformatics analysis. A gene expression dataset (GSE104793) was downloaded from the Gene Expression Omnibus. Bioinformatics analysis was then performed in order to identify differentially expressed genes (DEGs) between untreated chondrocytes and chondrocytes cultured with interleukin-1β (IL-1β) for 24 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape. A protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes. Gene set enrichment analysis (GSEA) was performed using GSEA software. Furthermore, chondrocytes were extracted and treated with IL-1β (10 ng/ml) for 24 h, and reverse-transcription quantitative PCR was used to confirm differential expression of hub genes. Patient samples were also collected to verify the bioinformatic analysis results. Based on the cut-off criteria used for determination of the DEGs, a total of 844 DEGs, including 498 upregulated and 346 downregulated DEGs, were identified. The DEGs were mainly enriched in the GO terms and KEGG pathways 'inflammatory response', 'negative regulation of cell proliferation', 'ossification', 'taxis', 'blood vessel morphogenesis', 'extracellular structure organization', 'mitotic cell cycle process' and 'TNF signaling pathway'. The majority of the PCR results, namely the differential expression of kininogen 2, complement C3, cyclin B1, cell division cycle 20, cyclin A2, 1-phosphatidylinositol 4-kinase, BUB1 mitotic checkpoint serine/threonine kinase, kinesin family member 11, cyclin B2 and BUB1 mitotic checkpoint serine/threonine kinase B were consistent with the bioinformatics results. Collectively, the present observations provided a regulation network of IL-1β-stimulated chondrocytes, which may provide potential targets of OA therapy.

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Identification of hub genes involved in the occurrence and development of hepatocellular carcinoma via bioinformatics analysis

Cited by 9 publications

References 60 publications

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma

Bioinformatics analysis and experimental validation of differentially expressed genes in mouse articular chondrocytes treated with IL‑1β using microarray data

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