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Identification of a Potential MiRNA-mRNA Regulatory Network for Osteoporosis by Using Bioinformatics Methods: A
Shi Lin1, Jianjun Wu1, Baixing Chen2
1The Third Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong, China.
Introduction:
As a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass, impairment of bone microstructure, and a high global morbidity rate. There is increasing evidence that microRNAs (miRNAs) are associated with the pathogenesis of OP. Weighted gene co-expression network analysis (WGCNA) is a systematic method for identifying clinically relevant genes involved in disease pathogenesis. However, the study of the miRNA-messenger RNA (mRNA) regulatory network in combination with WGCNA in OP is still lacking.
Methods:
The GSE93883 and GSE7158 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) were analyzed with the limma package. OP-related miRNAs from the most clinically relevant module were identified by the WGCNA method. The overlap of DE-miRNAs and OP-related miRNAs was identified as OP-related DE-miRNAs. Both upstream transcription factors and downstream targets of OP-related DE-miRNAs were predicted by FunRich. An intersection of predicted target genes and DEGs was confirmed as downstream target genes of OP-related DE-miRNAs. With the use of clusterProfiler in R, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on target genes. Finally, both the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed and analyzed.
Results:
A total of 79 OP-related DE-miRNAs were obtained, most of which were predicted to be regulated by specificity protein 1 (SP1). Subsequently, 197 downstream target genes were screened out. The target genes were enriched in multiple pathways, including signaling pathways closely related to the onset of OP, such as Ras, PI3K-Akt, and ErbB signaling pathways. Through the construction of the OP-related miRNA-mRNA regulatory network, a hub network that may play a prominent role in the formation of OP was documented.
Conclusion:
By using WGCNA, we constructed a potential OP-related miRNA-mRNA regulatory network, offering a novel perspective on miRNA regulatory mechanisms in OP.
Insights
This study identifies key microRNAs (miRNAs) and their target genes involved in osteoporosis (OP) pathogenesis using Weighted Gene Co-expression Network Analysis (WGCNA). The findings reveal a novel miRNA-mRNA regulatory network crucial for OP development.
Area of Science:
- Biomedical Research
- Genomics
- Molecular Biology
Background:
- Osteoporosis (OP) is a systemic skeletal disease with significant global morbidity.
- MicroRNAs (miRNAs) are increasingly implicated in the pathogenesis of OP.
- A comprehensive understanding of miRNA-messenger RNA (mRNA) regulatory networks in OP is lacking.
Purpose of the Study:
- To identify OP-related miRNAs and their downstream target genes.
- To construct and analyze a miRNA-mRNA regulatory network in osteoporosis.
- To elucidate novel miRNA regulatory mechanisms in OP pathogenesis.
Main Methods:
- Downloaded and analyzed microarray datasets (GSE93883, GSE7158) for differentially expressed miRNAs (DE-miRNAs) and genes (DEGs).
- Applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify OP-related miRNAs.
- Predicted upstream transcription factors and downstream targets, followed by pathway enrichment analysis (GO, KEGG) and network construction (PPI, miRNA-mRNA).
Main Results:
- Identified 79 OP-related DE-miRNAs, many regulated by SP1.
- Screened 197 downstream target genes enriched in OP-related pathways (Ras, PI3K-Akt, ErbB).
- Constructed a novel OP-related miRNA-mRNA regulatory network, highlighting potential key players in OP formation.
Conclusions:
- Developed a potential OP-related miRNA-mRNA regulatory network using WGCNA.
- Provided a novel perspective on miRNA regulatory mechanisms in osteoporosis.
- The identified network offers insights into the molecular basis of OP.
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