Dataset Information

Global Analysis of miRNA Signature Differentially Expressed in Insulin-resistant Human Hepatocellular Carcinoma Cell Line.

ABSTRACT: Chemoresistance mediated by insulin resistance (IR) in HCC has already been validated. However, the underlying mechanism, especially the involvement of microRNAs (miRNAs) was unelucidated. In this study, miRNA microarrays and bioinformatics methods were employed to determine the dysregulation of miRNA by IR in HCC cells, and quantitative RT-PCR (qRT-PCR) was applied to valid the miRNA array data. Of all the 2006 miRNAs screened, 32 miRNAs were found up or down regulated between the HepG2/IR cells and its parental cells. Further literature mining revealed that some of these miRNAs may function as oncogenes or tumor suppressors that contribute to tumor progression, recurrence, and metastasis which eventually lead to chemotherapeutic resistance. Interestingly, bioinformatics analysis by Gene Ontology (GO) enrichment pathway indicating that function of the predicted target genes of these dysregulated miRNAs were significantly enriched in the processes related with biosynthesis, catabolism, modification etc., and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping showed that the biological regulatory mechanisms were integrated in cancer-related pathways. Moreover, we also constructed a network which connected the differentially expressed miRNAs to target genes, GO enrichments and KEGG pathways to reveal the hub miRNAs, genes and pathways. Collectively, our present study demonstrated the possible miRNAs and predicted target genes involving in the pathophysiology of insulin resistant HCC, providing novel insights into the molecular mechanisms of multidrug resistance in the insulin resistant HepG2 cells.

SUBMITTER: Li L

PROVIDER: S-EPMC7085209 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Global Analysis of miRNA Signature Differentially Expressed in Insulin-resistant Human Hepatocellular Carcinoma Cell Line.

Li Linjing L Cheng Yan Y Lin Li L Liu Zhuan Z Du Shengfang S Ma Li L Li Jing J Peng Zhiheng Z Yan Jing J

International journal of medical sciences 20200224 5

Chemoresistance mediated by insulin resistance (IR) in HCC has already been validated. However, the underlying mechanism, especially the involvement of microRNAs (miRNAs) was unelucidated. In this study, miRNA microarrays and bioinformatics methods were employed to determine the dysregulation of miRNA by IR in HCC cells, and quantitative RT-PCR (qRT-PCR) was applied to valid the miRNA array data. Of all the 2006 miRNAs screened, 32 miRNAs were found up or down regulated between the HepG2/IR cell ...[more]

PMID: 32210717

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Project description:Background: Methylation plays a significant role in the etiology and pathogenesis of hepatocellular carcinoma (HCC). The aim of the present study is to identify aberrantly methylated-diferentially expressed genes (DEGs) and dysregulated pathways associated with the development of HCC through integrated analysis of gene expression and methylation microarray. Method: Aberrantly methylated-DEGs were identified from gene expression microarrays (GSE62232, GSE74656) and gene methylation microarrays (GSE44909, GSE57958). Functional enrichment and pathway enrichment analyses were performed through the database of DAVID. Protein-protein interaction (PPI) network was established by STRING and visualized in Cytoscape. Subsequently, overall survival (OS) analysis of hub genes was performed by OncoLnc. Finally, we validated the expression level of CDCA5 by quantitative real-time PCR (qRT-PCR) and western blotting, and performed Immunohistochemical experiments utilizing a tissue microarray. Cell growth assay and flow cytometry were behaved to explore the function of CDCA5. Results: Aberrantly methylated-DEGs were enriched in biological process, molecular function, cellular component and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among them, cell cycle was enriched most frequently, and some terms associated with cancer were enriched, such as p53 signaling pathway, pathways in cancers, PI3K-Akt signaling pathway and AMPK signaling pathway. After survival analysis and validation in TCGA database including methylation and gene expression status, 12 hub genes were identified. Furthermore, the expression level of new gene CDCA5 was validated in HCC cell lines and hepatic normal cell lines through qRT-PCR and western blotting. In additional, immunohistochemistry experiments revealed higher CDCA5 protein expression from HCC tumor tissues compared with paracancer tissues by tissue microarray. Finally, through loss of function, we demonstrated that CDCA5 promoted proliferation by regulating the cell cycle. Conclusions: In summary, the present study implied possible aberrantly methylated-differentially expressed genes and dysregulated pathways in HCC by bioinformatics analysis and experiments, which could be helpful in understanding the molecular mechanisms underlying the development and progression of HCC. Hub genes including CDC20, AURKB, BIRC5, RRM2, MCM2, PTTG1, CDKN2A, NEK2, CENPF, RACGAP1, GNA14 and especially the new gene CDCA5 may serve as biomarkers for diagnosis, treatment and prognosis of HCC.

Dataset Information

Global Analysis of miRNA Signature Differentially Expressed in Insulin-resistant Human Hepatocellular Carcinoma Cell Line.

Publications

Global Analysis of miRNA Signature Differentially Expressed in Insulin-resistant Human Hepatocellular Carcinoma Cell Line.

Similar Datasets

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