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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Gene Expression Microarray Data Meta-Analysis Identifies Candidate Genes and Molecular Mechanism Associated with
Ying Wang1, Haibin Wei2, Lizhi Song1
1Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Objective:
We aimed to explore potential molecular mechanisms of clear cell renal cell carcinoma (ccRCC) and provide candidate target genes for ccRCC gene therapy.
Materials And Methods:
This is a bioinformatics-based study. Microarray datasets of GSE6344, GSE781 and GSE53000 were downloaded from Gene Expression Omnibus database. Using meta-analysis, differentially expressed genes (DEGs) were identified between ccRCC and normal samples, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) function analyses. Then, protein-protein interaction (PPI) networks and modules were investigated. Furthermore, miRNAs-target gene regulatory network was constructed.
Results:
Total of 511 up-regulated and 444 down-regulated DEGs were determined in the present gene expression microarray data meta-analysis. These DEGs were enriched in functions like immune system process and pathways like Toll-like receptor signaling pathway. PPI network and eight modules were further constructed. A total of 10 outstanding DEGs including TYRO protein tyrosine kinase binding protein (TYROBP), interferon regulatory factor 7 (IRF7) and PPARG co-activator 1 alpha (PPARGC1A) were detected in PPI network. Furthermore, the miRNAs-target gene regulation analyses showed that miR-412 and miR-199b respectively targeted IRF7 and PPARGC1A to regulate the immune response in ccRCC.
Conclusion:
TYROBP, IRF7 and PPARGC1A might play important roles in ccRCC via taking part in the immune system process.
Insights
This bioinformatics study identified key genes, TYROBP, IRF7, and PPARGC1A, involved in clear cell renal cell carcinoma (ccRCC) immune responses. These findings offer potential targets for ccRCC gene therapy.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
- Understanding ccRCC molecular mechanisms is crucial for developing effective gene therapies.
Purpose of the Study:
- To explore molecular mechanisms of ccRCC using bioinformatics.
- To identify candidate target genes for ccRCC gene therapy.
Main Methods:
- Meta-analysis of ccRCC microarray datasets (GSE6344, GSE781, GSE53000).
- Identification of differentially expressed genes (DEGs) between ccRCC and normal samples.
- Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis.
- Construction of protein-protein interaction (PPI) networks and modules.
- Development of miRNA-target gene regulatory networks.
Main Results:
- Identified 511 up-regulated and 444 down-regulated DEGs.
- DEGs were enriched in immune system processes and Toll-like receptor signaling pathway.
- Constructed a PPI network with eight modules.
- Highlighted 10 key DEGs, including TYROBP, IRF7, and PPARGC1A.
- Discovered that miR-412 targets IRF7 and miR-199b targets PPARGC1A, regulating immune response in ccRCC.
Conclusions:
- TYROBP, IRF7, and PPARGC1A are potentially crucial in ccRCC pathogenesis.
- These genes may exert their influence through involvement in immune system processes.
- The study provides candidate genes for future ccRCC gene therapy strategies.
