Dataset Information

Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma.

ABSTRACT:

Background

Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment.

Methods

LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the median MYC expression level (high-MYC group and low-MYC group). Correlation analysis was performed to determine relationships between the expression of key MYC-associated genes and prognosis, DNA promotor methylation, and immune cell infiltration. Gene ontology and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analyses were performed to elucidate the functions of these genes in LIHC. Their expression and functions in LIHC were further verified using transgenic mice overexpressing c-Myc under control of the hepatocyte-specific promoter (Alb-Cre).

Results

AURKB, CCNB2, and CDKN3 were overexpressed in LIHC patients with high MYC expression and were associated with poor prognosis. Upregulation of these 3 genes was significantly correlated with hypomethylated promoter status, advanced T stage, metastasis, and immune cell infiltration in LIHC patients. Functional enrichment analyses indicated that these genes participate in the "p53 signaling pathway" and "cell cycle". Furthermore, RT-PCR and IHC analysis revealed that their mRNA and protein expression levels were upregulated in an Alb-Cre;cMYC^lsl/- mouse model. Drugs that target these 3 MYC-related genes were identified.

Conclusion

Taken together, our results identify biomarkers of potential utility for managing liver cancer therapy owing to their significance in tumorigenesis, proliferation, and tumor immunity.

SUBMITTER: Li S

PROVIDER: S-EPMC10703616 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma.

Li Sha S Xue Pei P Diao Xun X Fan Qi-Yu QY Ye Kun K Tang Xiao-Mei XM Liu Jia J Huang Zhong-Yan ZY Tang Qing-Hai QH Jia Cheng-You CY Xin Rui R Lv Zhong-Wei ZW Liu Ji-Bin JB Ma Yu-Shui YS Fu Da D

Journal of advanced research 20230127

<h4>Background</h4>Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment.<h4>Methods</h4>LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the ...[more]

PMID: 36716957

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Project description:BackgroundHepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC.MethodsGene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively.ResultsFifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05).ConclusionsCCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.

Dataset Information

Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma.

Background

Methods

Results

Conclusion

Publications

Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma.

Similar Datasets

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