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Published on: November 6, 2014
Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network
Zheng Wang1,2, Xiao-Fei Zhang3, Mao-Peng Wang1,2
1Department of Joint Surgery, Tianjin Hospital, Tianjin, China.
Objective:
To identify key pathological hub genes, micro RNAs (miRNAs), and circular RNAs (circRNAs) of osteoporosis (OP) and construct their ceRNA network in an effort to explore the potential biomarkers and drug targets for OP therapy.
Methods:
GSE7158, GSE201543, and GSE161361 microarray datasets were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by comparing OP patients with healthy controls and hub genes were screened by machine learning algorithms. Target miRNAs and circRNAs were predicted by FunRich and circbank, then ceRNA network were constructed by Cytoscape. Pathways affecting OP were identified by functional enrichment analysis. The hub genes were verified by receiver operating characteristic (ROC) curve and real time quantitative PCR (RT-qPCR). Potential drug molecules related to OP were predicted by DSigDB database and molecular docking was analyzed by autodock vina software.
Results:
A total of 179 DEGs were identified. By combining three machine learning algorithms, BAG2, MME, SLC14A1, and TRIM44 were identified as hub genes. Three OP-associated target miRNAs and 362 target circRNAs were predicted to establish ceRNA network. The ROC curves showed that these four hub genes had good diagnostic performance and their differential expression was statistically significant in OP animal model. Benzo[a]pyrene was predicted which could successfully bind to protein receptors related to the hub genes and it was served as the potential drug molecules.
Conclusion:
An mRNA-miRNA-circRNA network is reported, which provides new ideas for exploring the pathogenesis of OP. Benzo[a]pyrene, as potential drug molecules for OP, may provide guidance for the clinical treatment.
Insights
This study identifies key osteoporosis (OP) genes, microRNAs (miRNAs), and circular RNAs (circRNAs) to build a ceRNA network. Benzo[a]pyrene shows potential as a therapeutic drug for OP treatment.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Osteoporosis (OP) is a significant skeletal disorder.
- Identifying molecular players in OP pathogenesis is crucial for effective therapy.
Purpose of the Study:
- To identify key pathological hub genes, microRNAs (miRNAs), and circular RNAs (circRNAs) in osteoporosis.
- To construct a competing endogenous RNA (ceRNA) network for OP.
- To explore potential biomarkers and drug targets for osteoporosis therapy.
Main Methods:
- Downloaded and analyzed Gene Expression Omnibus (GEO) microarray datasets (GSE7158, GSE201543, GSE161361).
- Identified differentially expressed genes (DEGs) and screened hub genes using machine learning algorithms.
- Predicted target miRNAs and circRNAs, constructed the ceRNA network using Cytoscape, and performed functional enrichment analysis.
- Verified hub genes via receiver operating characteristic (ROC) curve and RT-qPCR; predicted and analyzed potential drug molecules using DSigDB and molecular docking.
Main Results:
- Identified 179 DEGs, with BAG2, MME, SLC14A1, and TRIM44 identified as hub genes.
- Established an mRNA-miRNA-circRNA ceRNA network involving 3 target miRNAs and 362 target circRNAs.
- Hub genes demonstrated good diagnostic performance and significant differential expression in an OP animal model.
- Benzo[a]pyrene was predicted as a potential drug molecule that binds to relevant protein receptors.
Conclusions:
- An mRNA-miRNA-circRNA network offers novel insights into osteoporosis pathogenesis.
- Benzo[a]pyrene presents potential as a therapeutic agent for osteoporosis, guiding clinical treatment.
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