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Investigation of microRNA expression signatures in HCC via microRNA Gene Chip and bioinformatics analysis
Affiliation:1. Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China;2. Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China;3. Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China;1. Department of Biomedical Sciences, Department of Physiology, University of Ulsan College of Medicine, Seoul, South Korea;2. Asan Medical Center, Seoul, South Korea;3. Stem Cell Regulation and Animal Aging Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, USA;1. Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China;2. The Fourth Clinical School of Nanjing Medical University, Nanjing 210029, China;3. Department of Oncology, Xuzhou Medical College, Xuzhou 221004, China;4. Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China;1. National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India;2. School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India;3. Department of Microbiology and Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19,104, United States
Abstract:BackgroundDysregulation of miRNAs is closely involved with hepatocellular carcinoma (HCC) progression, oncogenesis and signalling pathways. The aim of this study was to investigate differences in expression of miRNAs in HCC tissue in comparison to healthy liver tissue, as well as to explore the key miRNA-targeted genes.MethodsGene Chip microarray analysis was used to analyse differentially expressed miRNAs (DEMs) in tissues, and qRT-PCR was performed to validate the top 9 downregulated miRNAs. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed for target genes using the DAVID database. A protein-protein interaction (PPI) network of the target genes was created by STRING and visualised using Cytoscape. Three online miRNA databases were utilised to aid in the prediction of genes targeted by the top 10 significantly altered DEMs.ResultsIn total, 153 upregulated and 206 downregulated miRNAs were identified in HCC tissue. The genes targeted by the top 10 increased and decreased miRNAs were 6 and 1060, respectively. Moreover, FOXO1 was projected to be regulated by all twenty miRNAs. A PPI network was constructed that consisted of 956 nodes and 1298 edges. Four significant modules, consisting of 66 hub genes, were detected from the PPI system via MCODE. Functional enrichment demonstrated that miRNAs have a vital function in cancer development and advancement.ConclusionIn summary, our study identified DEMs in HCC tissue, major target genes and possible molecular mechanisms that underlie HCC, providing novel insights for treatment approaches.
Keywords:hepatocellular carcinoma  differentially expressed microRNAs  functional enrichment  bioinformatics analysis
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