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. 2018 Sep;16(3):1841-1849.
doi: 10.3892/etm.2018.6360. Epub 2018 Jun 27.

Integrated analysis of key mRNAs and lncRNAs in osteoarthritis

Lei Chen  1 , Yingqi Zhang  1 , Zhitao Rao  1 , Jincheng Zhang  1 , Yeqing Sun  1
Affiliations

Integrated analysis of key mRNAs and lncRNAs in osteoarthritis

Lei Chen et al. Exp Ther Med. 2018 Sep.

Abstract

Osteoarthritis (OA) is the most common type of arthritis, observed mainly in the population aged >65 years. However, the mechanism underlying the development and progression of OA has remained largely elusive. The present study aimed to identify differentially expressed mRNAs and lncRNAs in OA. By analyzing the GSE48556 and GSE82107 datasets, a total of 202 up- and 434 downregulated mRNAs were identified in OA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that differently expressed genes were mainly involved in regulating antigen processing and presentation, interspecies interaction between organisms, immune response, transcription and signal transduction. In addition, a series of long non-coding (lnc)RNAs were differently expressed in OA. To provide novel data on the molecular mechanisms and functional roles of these lncRNAs in OA, a co-expression analysis was performed, which revealed that the dysregulated lncRNAs were associated with transcription, signal transduction, immune response and cell adhesion. In addition, certain key genes in protein-protein interaction networks were identified. The present study provided useful information for exploring potential candidate biomarkers for the diagnosis and prognosis of OA, as well as novel drug targets.

Keywords: differentially expressed gene; expression profiling; long non-coding RNA; osteoarthritis; protein-protein interaction network.

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Figures

Figure 1.
Figure 1.
Clustering analysis of differentially expressed mRNAs between osteoarthritis patients and healthy controls in the datasets (A) GSE48556 and (B) GSE82107. Integrated analysis of (C) upregulated and (D) downregulated mRNAs.
Figure 2.
Figure 2.
GO and KEGG pathway analysis of differentially expressed mRNAs. (A) GO analysis and (B) KEGG analysis of upregulated mRNAs in OA-associated biological processes and pathways, respectively. (C) GO analysis and (D) KEGG analysis of downregulated mRNAs in OA-associated biological processes and pathways, respectively. GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; OA, osteoarthritis; ER, endoplasmic reticulum; ECM, extracellular matrix; VEGF, vascular endothelial growth factor; MAPK, mitogen-activated protein kinase; GnRH, gonadotropin-releasing hormone; SNARE, soluble NSF attachment protein receptor.
Figure 3.
Figure 3.
Protein-protein interaction networks of (A) upregulated and (B) downregulated genes in osteoarthritis patients.
Figure 4.
Figure 4.
Hub modules from the PPI network in osteoarthritis patients were constructed. (A) A total of five upregulated proteins constituted a hub PPI module: GOSR1, SEC22C, VAMP7, STX16) and VAMP3. (B and C) Twelve downregulated proteins constituted 2 hub PPI modules: CCL5, GAL, CXCL5, APP, ADCY9, HRH4, CXCR5, RPA1, RAD50, DNA2, RAD17 and RECQL5. PPI, protein-protein interaction. GOSR1, golgi SNAP receptor complex member 1; SEC22C, SEC22 homolog C vesicle trafficking protein; VAMP7, vesicle associated membrane protein 7; STX16, syntaxin 16; VAMP3, vesicle associated membrane protein 3; CCL5, C-C motif chemokine ligand 5; GAL, galanin and GMAP prepropeptide; CXCL5, C-X-C motif chemokine ligand 5; APP, amyloid beta precursor protein; ADCY9, adenylate cyclase 9; HRH4, histamine receptor H4; CXCR5, C-X-C motif chemokine receptor 5; RPA1, replication protein A1; RAD50, RAD50 double strand break repair protein; DNA2, DNA replication helicase/nuclease 2; RAD17, RAD17 checkpoint clamp loader component; RECQL5, RecQ like helicase 5.
Figure 5.
Figure 5.
(A) Differentially expressed gene-lncRNA co-expression pairs with an absolute value of the Pearson correlation coefficient of ≥0.9 were selected. (B) Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of lncRNAs based on the set of co-expressed mRNAs. OA, osteoarthritis; lncRNA, long non-coding RNA; ER, endoplasmic reticulum; ECM, extracellular matrix; MAPK, mitogen-activated protein kinase; Jak, Janus kinase; STAT, signal transducer and activator of transcription; LINC00592, long intergenic non-protein coding RNA 592; LINC00960, long intergenic non-protein coding RNA 960; LINC00934, long intergenic non-protein coding RNA 934; BANCR, BRAF-activated non-protein coding RNA; CBR3-AS1, CBR3 antisense RNA 1; SEC24B-AS1, SEC24B antisense RNA 1; HCG18, HLA complex group 18 (non-protein coding); EIF1B-AS1, EIF1B antisense RNA 1; ELOVL2-AS1, ELOVL2 antisense RNA 1; LINC00276, long intergenic non-protein coding RNA 276; RAD21-AS1, RAD21 antisense RNA 1; MIR3610, microRNA 3610; LINC00669, MIR924 host gene; FLJ2276, chromosome 3 open reading frame 85; LINC00102, long intergenic non-protein coding RNA 102.
Figure 6.
Figure 6.
Co-expression networks for key long non-coding RNAs in osteoarthritis. The co-expression networks were constructed for (A) RAD21-AS1, (B) MCM3AP-AS1, (C) EIF1B-AS1, (D) LOC101929268, (E) ELOVL2-AS1 and (F) LINC00276. RAD21-AS1, RAD21 antisense RNA 1; MCM3AP-AS1, MCM3AP antisense RNA 1; EIF1B-AS1, EIF1B antisense RNA 1; ELOVL2-AS1, ELOVL2 antisense RNA 1; LINC00276, long intergenic non-protein coding RNA 276.
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