Abstract
Purpose To identify pivotal differentially expressed miRNAs and genes and construct their regulatory network in hepatocellular carcinoma. Methods mRNA (GSE101728) and microRNA (GSE108724) microarray datasets were obtained from the NCBI Gene Expression Omnibus (GEO) database. Then, we identified the differentially expressed miRNAs and mRNAs. Sequentially, transcription factor enrichment and gene ontology (GO) enrichment analysis for miRNA were performed. Target genes of these differential miRNAs were obtained using packages in R language (R package multiMiR). After that, downregulated miRNAs were matched with target mRNAs which were upregulated, while upregulated miRNAs were paired with downregulated target mRNA using scripts written in Perl. An miRNA-mRNA network was constructed and visualized in Cytoscape software. For miRNAs in the network, survival analysis was performed. And for genes in the network, we did gene ontology (GO) and KEGG pathway enrichment analysis. Results A total of 35 miRNAs and 295 mRNAs were involved in the network. These differential genes were enriched in positive regulation of cell-cell adhesion, positive regulation of leukocyte cell-cell adhesion, and so on. Eight differentially expressed miRNAs were found to be associated with the OS of patients with HCC. Among which, miR-425 and miR-324 were upregulated while the other six, including miR-99a, miR-100, miR-125b, miR-145, miR-150, and miR-338, were downregulated. Conclusion In conclusion, these results can provide a potential research direction for further studies about the mechanisms of how miRNA affects malignant behavior in hepatocellular carcinoma.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world
The development of HCC is closely related to the infection of the hepatitis B virus (HBV) infection, followed by the hepatitis C virus infection (HCV), and related to aflatoxins, alcohol drinking, and so on [4, 5]
The GSE101728 dataset was composed of seven pairs of HCC and matched adjacent tumor-free tissue sample mRNA expression profiles which were collected during the surgery from HCC patients admitted to the Zhongshan Hospital of Fudan University [13]
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. It is estimated that 840,000 new cases of HCC are acquired and at least 780,000 people die of HCC every year, and over half of the global incidence and mortality of HCC occur especially in Eastern Asian [1]. HCC has a high incidence (4.7% of new cancer cases) and the second highest cancer mortality rate (8.2% of cancer-related deaths) worldwide [2], and China accounts for 47% of the total number of HCC cases as well as HCC-related mortality [3]. In China, HCC has the third highest cancer incidence and has become the second leading cause of cancer-related death, second only to lung cancer [6]. There are many difficulties in the diagnosis and treatment of HCC, but the most frequent is the lack of methods for early diagnosis as well as the paucity of studies about the molecular mechanisms of tumor initiation and progression. We designed the study to explore the molecular mechanisms of HCC carcinogenesis and progression, as well as new relevant molecular markers for early diagnosis
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