microRNA-9 might be a novel protective factor for osteoarthritis patients

Abstract

Background: The study aimed to identify the targeting genes and miRNAs using the microarray expression profile dataset for Osteoarthritis (OA) patients. Differentially expressed genes (DEGs) between OA and control samples were identified using Bayes method of limma package. Subsequently, a protein-protein interaction (PPI) network was constructed. miRNAs and transcription factor (TFs) based on DEGs in PPI network were identified using Webgestalt and ENCODE, respectively. Finally, MCODE, Gene Ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. The expressions of several DEGs and predicted miRNAs in OA rats were detected by RT-PCR.

Results: A total of 594 DEGs were identified. In PPI network, there were 313 upregulated DEGs and 22 downregulated DEGs. Besides, the regulatory relationships included 467 upregulated interactions and 85 downregulated interactions (miR-124A → QKI and MAP 1B) between miRNA and DEGs in PPI network. The module from downregulated DEGs-TFs-miRNA networks was mainly enriched to low-density lipoprotein particle clearance, response to linoleic acid, and small molecule metabolic process BP terms. Moreover, QKI, MAP 1B mRNA and miR-9 expressions were significantly reduced in OA rats.

Conclusion: miR-9 might be a protective factor for OA patients via inhibiting proliferation and differentiation of cartilage progenitor cells. miR-124A might play an important role in progression of OA through targeting QKI and MAP 1B.

Keywords: Modules, protective factor; Osteoarthritis; Protein-protein interaction; microRNAs.

Fig. 1

The protein-protein interaction (PPI) network for upregulated differentially expressed genes (DEGs) (a) and downregulated DEGs (b). Red nodes indicate upregulated DEGs, green nodes indicate downregulated DEGs, and the black lines indicate the interactions. The node is larger, and it degree is higher, suggesting that it has more interactions with other proteins in PPI network

Fig. 2

The integrated network based on upregulated DEGs, transcription factor (TFs), and miRNA. Red circles indicate DEGs, green triangles indicate TFs, and blue rhombus indicate miRNAs. Arrows indicate transcriptional regulatory relationship, T-type lines indicate miRNA regulation relationship, straight lines indicate PPIs

Fig. 3

The integrated network based on downregulated DEGs, transcription factor (TFs), and miRNA. Green circles indicate DEGs, red triangles indicate TFs, and blue rhombus indicate miRNAs. Arrows indicate transcriptional regulatory relationship, T-type lines indicate miRNA regulation relationship, straight lines indicate PPIs

Fig. 4

The significant network module with the highest Mcode score (5.739) from the upregulated DEGs-TFs-miRNA integrated network and the module (Mcode score = 6.667) from the downregulated DEGs-TFs-miRNA integrated network. Red nodes indicate upregulated DEGs, green nodes indicate downregulated DEGs

Fig. 5

The relative expressions of miR-9, QKI and MAP 1B. *P < 0.05 indicates that there is significantly different between control and OA samples. **P < 0.01