Abstract
BackgroundThe aim of the current study was to investigate the long non-coding RNA (lncRNA) expression profiles in psoriatic arthritis (PSA) patients by RNA sequencing, and to further explore potential biomarkers that were able to predict PSA risk and activity.MethodsLncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMC) of 4 PSA patients and 4 normal controls (NCs) were detected by RNA sequencing, followed by comprehensive bioinformatic analyses. Subsequently, 3 top upregulated and 2 top downregulated lncRNAs were chosen for further validation in 93 PSA patients and 93 NCs by quantitative polymerase chain reaction (qPCR) assay.ResultsTotally 76 upregulated and 54 downregulated lncRNAs, as well as 231 upregulated and 102 downregulated mRNAs were discovered in PSA patients compared with NCs. Enrichment analyses revealed that they were mostly associated with nucleosome, extracellular exosome and extracellular matrix, and the top enriched pathways were systemic lupus erythematosus (SLE), alcoholism and viral carcinogenesis. qPCR assay showed that lnc-RP11-701H24.7 and lnc-RNU12 were upregulated in PSA patients compared with NCs, and they could predict PSA risk with high area under curves. Besides, lnc-RP11-701H24.7 was positively associated with ESR, SJC, TJC and pain VAS score while lnc-RNU12 was positively correlated with PASI score, CRP and PGA score, implying that both of them were positively correlated with disease activity.ConclusionOur study facilitates comprehensive understanding of lncRNA expression profiles in PSA pathogenesis, and discovers that lnc-RP11-701H24.7 and lnc-RNU12 might be served as novel biomarkers for PSA risk and activity.
Highlights
The aim of the current study was to investigate the long non-coding RNA expression profiles in psoriatic arthritis (PSA) patients by RNA sequencing, and to further explore potential biomarkers that were able to predict PSA risk and activity
Principal component analysis (PCA) plot and heatmap analysis of long non-coding RNA (lncRNA) and mRNA profiles To determine whether these 8 samples of PSA patients and normal controls (NCs) could be grouped, PCA was performed, which showed a clear segregation between 4 PSA patients and 4 NCs by lncRNA profiles (Fig. 2a)
Volcano plot and heatmap analysis for differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) A total of 10,079 lncRNAs which were detected in no less than 50% of samples were identified and included into analysis, 76 remarkably upregulated and 54 remarkably downregulated lncRNAs were found in PSA patients compared with NCs using Benjamini & Hochberg (BH) adjusted method (p < 0.05 and fold change≥2) (Fig. 3a)
Summary
The aim of the current study was to investigate the long non-coding RNA (lncRNA) expression profiles in psoriatic arthritis (PSA) patients by RNA sequencing, and to further explore potential biomarkers that were able to predict PSA risk and activity. Long non-coding RNA (lncRNA), a class of RNAs that have more than 200 nucleotides and lack open reading frames, is implicated different cancers, CAD and autoimmune diseases [7, 8]. An interesting study investigates the lncRNA expression profiles in T cells of SLE patients using microarray, which finds 1935 differentially expressed lncRNAs (DELs) in SLE patients compared with healthy controls (HCs), further analyses reveal that both uc001ykl. and ENST00000448942 expressions could differentiate SLE patients from controls and positively correlate with disease activity as well as inflammation level [9]. LncRNA expression profiles in peripheral blood mononuclear cells (PBMC) of RA patients are investigated, 5045 DELs are identified in RA patients compared with HCs, enrichment analyses indicate that these DELs are mostly implicated bile secretion, T cell receptor signaling pathways and SLE [10]
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