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. 2019 Mar;43(3):1179-1192.
doi: 10.3892/ijmm.2018.4038. Epub 2018 Dec 20.

Identification of the key genes and long non‑coding RNAs in ankylosing spondylitis using RNA sequencing

Zhengkuan Xu  1 , Hao Li  1 , Qixin Chen  1 , Gang Chen  1
Affiliations

Identification of the key genes and long non‑coding RNAs in ankylosing spondylitis using RNA sequencing

Zhengkuan Xu et al. Int J Mol Med. 2019 Mar.

Erratum in

Abstract

Ankylosing spondylitis (AS) is an insidious and debilitating form of arthritis that involves the axial skeleton, and its etiology and pathogenesis remain unclear. In the present study, three patients with AS and three normal controls from our hospital were enrolled. RNA sequencing and bioinformatics analysis were performed in order to identify the differentially expressed (DE) mRNAs (DEmRNAs) and DE long non‑coding RNAs (DElncRNAs) between the patients with AS and normal controls. Construction of an AS‑specific protein‑protein interaction network, a weighted DElncRNA‑DEmRNA co‑expression network and functional annotation of the DEmRNAs co‑expressed with DElncRNAs was performed. Nearby cis‑targeted DEmRNAs or DElncRNAs were identified by searching for DEmRNAs that were transcribed within 100‑kb up‑ or downstream of DElncRNAs. Based on the Gene Expression Omnibus datasets GSE25101 and GSE73754, the expression of selected DEmRNAs and DElncRNAs were verified using published RNA sequencing data from blood samples, and receiver operating characteristic analysis of selected DEmRNAs was performed. Compared with the normal controls, 1,072 DEmRNAs and 372 DElncRNAs in the patients with AS were identified. Caspase recruitment domain family member 11 and DNA methyltransferase 1 have great diagnostic value for AS. MSTRG.8559 and LINC00987 were also identified as two hub DElncRNAs. The T‑cell receptor signaling pathway was a significantly enriched pathway of the DEmRNAs co‑expressed with DElncRNAs in patients with AS. In conclusion, the present study identified the key DEmRNAs and DElncRNAs in AS, which provides novel information for understanding the pathogenesis of AS and developing potential biomarkers for AS.

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Figures

Figure 1
Figure 1
AS-specific PPI network. Blue and red shapes represent proteins encoded by down- and upregulated DEmRNAs, respectively, when comparing patients with AS and normal controls. Among these, blue shapes with green outlines represent proteins encoded by the top 10 downregulated DEmRNAs; red shapes with red outlines represent proteins encoded by the top 10 upregulated DEmRNAs. AS, ankylosing spondylitis; DEmRNA, differentially expressed mRNA.
Figure 2
Figure 2
Selected DElncRNA-DEmRNA co-expression network. Ovals and rhombuses represent DEmRNAs and DElncRNAs, respectively, comparing AS patients and normal controls. Shapes with bold black outlines indicate the top 10 DEmRNAs/DElncRNAs when comparing AS and normal controls. AS, ankylosing spondylitis; DEmRNA, differentially expressed mRNA; DElncRNA, differentially expressed long non-coding RNA.
Figure 3
Figure 3
Top 15 most significantly enriched GO terms of DEmRNAs co-expressed with DElncRNAs. The x-axis presents the number of DEmRNAs enriched in the GO terms and the y-axis presents the GO terms. (A) Biological process; (B) Cellular component; (C) Molecular function. GO, Gene Ontology; DEmRNA, differentially expressed mRNA; DElncRNA, differentially expressed long non-coding RNA; FDR, false discovery rate.
Figure 4
Figure 4
Top 15 most significantly enriched KEGG pathways of DEmRNAs co-expressed with DElncRNAs. The x-axis presents the number of DEmRNAs enriched in KEGG pathways and the y-axis presents the KEGG pathways. KEGG, Kyoto Encyclopedia of Genes and Genomes; DEmRNA, differentially expressed mRNA; DElncRNA, differentially expressed long non-coding RNA; FDR, false discovery rate.
Figure 5
Figure 5
Validation the expression of selected DEmRNAs between patients with AS and normal controls in the GSE73754 dataset. The x-axis presents the AS and normal control groups and the y-axis presents the expression levels of (A) CARD11, (B) DNMT1, (C) PDCD1 and (D) PLCG1. Data are presented as the median and the 75th and 25th percentiles. *P<0.05 vs. control. AS, ankylosing spondylitis; DEmRNA, differentially expressed mRNA; CARD11, caspase recruitment domain-containing protein 11; DNMT1, DNA methyltransferase 1; PDCD1, programmed cell death 1; PLCG1, phospholipase Cγ1.
Figure 6
Figure 6
Validation of the expression of selected DEmRNAs and DElncRNAs between patients with AS and the normal controls in the GSE25101 dataset. The x-axis presents the AS and normal control groups and the y-axis presents the expression levels. (A) The selected DEmRNAs and (B) The selected DElncRNAs. AS, ankylosing spondylitis; DEmRNA, differentially expressed mRNA; DElncRNA, differentially expressed long non-coding RNA; CARD11, caspase recruitment domain-containing protein 11; DNMT1, DNA methyltransferase 1; PDCD1, programmed cell death 1; PLCG1, phospholipase Cγ1; MANSC1, MANSC domain containing 1; ATP2A2, adenosine triphosphatase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2; MZF1, myeloid zinc finger 1; CECR7, cat eye syndrome chromosome region candidate 7; HYMAI, hydatidiform mole associated and imprinted.
Figure 7
Figure 7
ROC curves of CARD11 and DNMT1 comparing patients with ankylosing spondylitis and normal controls in the GSE73754 dataset. ROC curves displayed the diagnostic ability of differentially expressed long non-coding RNA with sensitivity (the proportion of true positive) and 1-Specificity (the proportion of false positive). The x-axis presents 1-specificity and y-axis presents sensitivity. (A) CARD11 and (B) DNMT1. ROC, receiver operating characteristic; CARD11, caspase recruitment domain-containing protein 11; DNMT1, DNA methyltransferase 1; AUC, area under the curve.
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