通过 RNA 测序对长非编码 RNA 表达谱进行全面分析，并探讨其在银屑病关节炎患者作为生物标志物的潜力。
Comprehensive analyses of long non-coding RNA expression profiles by RNA sequencing and exploration of their potency as biomarkers in psoriatic arthritis patients.
机构信息
Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, 540 Xinhua Road, Shanghai, 200052, China.
Department of Dermatology, Skin Disease Prevention and Treatment of Fengxian District of Shanghai, Shanghai, China.
出版信息
BMC Immunol. 2019 Aug 7;20(1):28. doi: 10.1186/s12865-019-0297-9.
BACKGROUND
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.
METHODS
LncRNA 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.
RESULTS
Totally 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.
CONCLUSION
Our 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.
背景
本研究旨在通过 RNA 测序技术分析银屑病关节炎（PSA）患者的长链非编码 RNA（lncRNA）表达谱，并进一步探讨潜在的生物标志物，以预测 PSA 的发病风险和疾病活动度。
方法
采用 RNA 测序技术检测 4 例 PSA 患者和 4 例健康对照者（NCs）外周血单个核细胞（PBMC）中的 lncRNA 和 mRNA 表达谱，然后进行全面的生物信息学分析。随后，在 93 例 PSA 患者和 93 例 NCs 中，通过定量聚合酶链反应（qPCR）实验验证了 3 个上调最显著和 2 个下调最显著的 lncRNA。
结果
与 NCs 相比，PSA 患者中共有 76 个上调和 54 个下调的 lncRNA，以及 231 个上调和 102 个下调的 mRNA。富集分析显示，这些 lncRNA 和 mRNA 主要与核小体、细胞外外泌体和细胞外基质有关，最富集的通路为系统性红斑狼疮（SLE）、酒精中毒和病毒致癌作用。qPCR 实验结果显示，与 NCs 相比，lnc-RP11-701H24.7 和 lnc-RNU12 在 PSA 患者中表达上调，且具有较高的曲线下面积，可用于预测 PSA 发病风险。此外，lnc-RP11-701H24.7 与 ESR、SJC、TJC 和疼痛 VAS 评分呈正相关，而 lnc-RNU12 与 PASI 评分、CRP 和 PGA 评分呈正相关，表明两者均与疾病活动度呈正相关。
结论
本研究有助于全面了解 lncRNA 在 PSA 发病机制中的表达谱，并发现 lnc-RP11-701H24.7 和 lnc-RNU12 可能作为 PSA 发病风险和疾病活动度的新型生物标志物。
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