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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.
Orthopaedic Surgery
|December 13, 2022
Summary
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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