Altered blood and keratinocyte microRNA/transfer RNA fragment profiles related to fibromyalgia syndrome and its severity.

IF 5.9 1区 医学 Q1 ANESTHESIOLOGY
Christoph Erbacher, Shani Vaknine-Treidel, Nimrod Madrer, Sofia Weinbender, Dimitar Evdokimov, Stefan Unterecker, Gilli Moshitzky, Claudia Sommer, David S Greenberg, Hermona Soreq, Nurcan Üçeyler
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Abstract

Abstract: Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls). Small RNAs were quantified via RNA-sequencing and candidates validated via qRT-PCR. MicroRNAs and tRFs were tested for association with FMS symptoms and their potential regulatory roles. miR and tRF profiles were altered in FMS compared to hCO in whole blood (n = 69; n = 22) and keratinocytes (n = 41; n = 55). Receiver operating characteristic analysis of blood miR candidates hsa-miR-148a-3p and hsa-miR-182-5p, and tRF candidate tRF-21-WB8647O5D levels separated FMS from hCO. In blood, hsa-miR-182-5p and hsa-miR-576-5p upregulation was validated via qRT-PCR, showing even higher expression in disease control, while TRF-20-40KK5Y93 was selectively increased in FMS. MicroRNAs in blood and keratinocytes were associated with how widespread pain manifested in patients. Keratinocyte tRFs correlated with loss of skin innervation. In blood, altered small RNAs were linked to immune and RNA processes, whereas in keratinocytes, adhesion and epithelial functions were targeted. Modulated tRFs shared sequence motifs in patients with FMS, which may promote concerted pathway regulation. Our findings show miRs/tRFs as key small RNAs dysregulation in FMS pathophysiology and open new perspectives for FMS diagnostics, symptom monitoring, and clinical management.

与纤维肌痛综合征及其严重程度有关的血液和角质细胞微RNA/转移RNA片段特征的改变。
摘要:纤维肌痛综合征(FMS)是一种病理生理学尚不清楚的使人衰弱的广泛性慢性疼痛。我们研究了作为 FMS 潜在分类器和介质的小非编码 RNA。我们通过小 RNA 测序对 53 名 FMS 患者与 34 名健康对照组(hCOs)和 15 名重度抑郁症和慢性身体疼痛患者(疾病对照组)组成的全面表型女性队列中的血液和角质细胞微 RNA(miRs)和转移 RNA 片段(tRFs)进行了分析。通过 RNA 测序对小 RNA 进行量化,并通过 qRT-PCR 对候选 RNA 进行验证。在全血(n = 69;n = 22)和角质细胞(n = 41;n = 55)中,FMS 的 miR 和 tRF 图谱与 hCO 相比发生了改变。血液 miR 候选者 hsa-miR-148a-3p 和 hsa-miR-182-5p 以及 tRF 候选者 tRF-21-WB8647O5D 水平的接收器操作特征分析将 FMS 与 hCO 区分开来。在血液中,hsa-miR-182-5p 和 hsa-miR-576-5p 的上调通过 qRT-PCR 得到了验证,在疾病控制中显示出更高的表达,而 TRF-20-40KK5Y93 在 FMS 中选择性地增加。血液和角质细胞中的微RNA与患者广泛疼痛的表现形式有关。角质细胞的tRFs与皮肤神经支配的丧失有关。在血液中,改变的小 RNA 与免疫和 RNA 过程有关,而在角质形成细胞中,则针对粘附和上皮功能。受调控的 tRFs 在 FMS 患者中具有共同的序列基序,这可能会促进协调的通路调控。我们的研究结果表明,miRs/tRFs 是 FMS 病理生理学中关键的小 RNAs 失调,为 FMS 诊断、症状监测和临床管理开辟了新的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PAIN®
PAIN® 医学-临床神经学
CiteScore
12.50
自引率
8.10%
发文量
242
审稿时长
9 months
期刊介绍: PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.
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