Abstract
Background
This study aimed to analyze long non-coding RNA (lncRNA) expression profiles in synovium tissue of patients with RA using RNA sequencing, and to further assess the clinical values of dysregulated lncRNAs in RA diagnosis and monitoring.
Methods
Thirty patients with RA who underwent knee arthroscopy and 30 controls with knee trauma who underwent surgery were consecutively enrolled and synovium tissue samples of both groups were obtained during surgery. In the exploration stage, lncRNA and mRNA expression profiles in three RA samples and three control samples were detected by RNA sequencing and bioinformatic analyses were then performed. In the validation stage, quantitative polymerase chain reaction (qPCR) was subsequently used to detect expression of five candidate lncRNAs in 30 patients with RA and 30 control patients.
Results
A total of 349 lncRNAs and 1582 mRNAs were upregulated and 806 lncRNAs and 1295 mRNAs were downregulated in patients with RA compared with controls. Enrichment analyses revealed that these dysregulated lncRNAs and mRNAs were mainly involved in regulating immune response, leukocyte migration, complement activation, and B cell receptor signaling pathway. Subsequent qPCR validation discovered that lnc-AL928768.3 (P < 0.001) and lnc-AC091493.1 (P < 0.001) were elevated in patients with RA compared with controls and afford good predictive values for RA risk by receiver operating characteristic (ROC) curve analysis. Additionally, the two lncRNAs were positively associated with C-reactive protein level and disease activity score in 28 joints (ESR) (all P < 0.05).
Conclusion
Analysis of lncRNA expression profiles by sequencing reveals that lnc-AL928768.3 and lnc-AC091493.1 are novel biomarkers for RA risk and activity.
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Acknowledgements
This study was supported by the Science and Technology Project of Wenzhou (Y20170060 and Y20170056), Science and Technology Action Plan for Major Disease Control-Trauma Repair Special Project, National Health and Family Planning Commission Medical Science and Technology Development Research Center (ZX-01-C2016029), Medical Science Research Foundation of Zhejiang Province, China (no. 2020374759).
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This study was approved by the Ethics Review Board of The First Affiliated Hospital of Wenzhou Medical University, and all participants provided written informed consent before enrollment. The ethical approval number was 2015-06-03.
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Sun, L., Tu, J., Liu, C. et al. Analysis of lncRNA expression profiles by sequencing reveals that lnc-AL928768.3 and lnc-AC091493.1 are novel biomarkers for disease risk and activity of rheumatoid arthritis. Inflammopharmacol 28, 437–450 (2020). https://doi.org/10.1007/s10787-019-00666-6
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DOI: https://doi.org/10.1007/s10787-019-00666-6