Microarray-based measurement of microRNA-449c-5p levels in hepatocellular carcinoma and bioinformatic analysis of potential signaling pathways
| Autor: | Li Jiang, Chang-Liang Wu, Guo-Jian Li, Xia Yang, Han-lin Wang, Ji-Zhou Wu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Microarray In silico Human Protein Atlas Down-Regulation Computational biology Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor microRNA Humans Gene Cell Proliferation DNA Polymerase III Liver Neoplasms Computational Biology Cell Biology Transfection Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis DNA microarray |
| Zdroj: | Pathology, research and practice. 215(1) |
| ISSN: | 1618-0631 |
| Popis: | The clinical role and potential molecular mechanisms of microRNA-449c-5p (miR-449c-5p) in hepatocellular carcinoma (HCC) tissues remains unclear. Combining multiple bioinformatic tools, we studied the miR-449c-5p expression levels in HCC tissues and explored possible target genes and related signaling pathways. First, miR-449c-5p expression data from microarrays provided by publicly available sources were mined and analyzed using various meta-analysis methods. Next, genes that were downregulated after miR-449c-5p mimic transfection into HCC cells were identified, and in silico methods were used to predict potential target genes. Several bioinformatic assessments were also performed to evaluate the possible signaling pathways of miR-449c-5p in HCC. Five microarrays were included in the current study, including GSE98269, GSE64632, GSE74618, GSE40744 and GSE57555. The standard mean difference was 0.44 (0.07-0.80), and the area under the curve was 0.68 (0.63-0.72), as assessed by meta-analyses, which consistently indicated the upregulation of miR-449c-5p in HCC tissues. A total of 2244 genes were downregulated after miR-449c-5p mimic transfection into an HCC cell line, while 5217 target genes were predicted by in silico methods. The overlap of these two gene pools led to a final group of 428 potential target genes of miR-449c-5p. These 428 potential target genes were primarily enriched in the homologous recombination pathway, which includes DNA Polymerase Delta 3 (POLD3). Data mining with Oncomine and the Human Protein Atlas showed a decreasing trend in POLD3 mRNA and protein levels in HCC tissue samples. This evidence suggests that miR-449c-5p could play an essential role in HCC through various pathways and that POLD3 could be a potential miR-449c-5p target. However, these in silico findings should be validated with further experiments. |
| Databáze: | OpenAIRE |
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