Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis
Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis
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DOI：
10.1016/j.joca.2020.07.003
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发表时间：
2020-11-01
影响因子：
7
通讯作者：
Kapoor, M.
中科院分区：
文献类型：
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作者：
Ali, S. A.;Gandhi, R.;Kapoor, M.
目的：microRNA在局部和全身作用以影响骨关节炎（OA）病理生理学，但尚未对OA早期与晚期的循环microRNA组进行全面分析。测序已成为microRNA分析的首选方法，因为它提供了高灵敏度和特异性。我们的目的是对来自91名患有早期[KellgreneLawrence（KL）0级或1级（n = 41）]或晚期[KL 3级或4级（n = 50）]症状性放射学膝OA的患者的血浆中的miRNome进行测序，以鉴定每种疾病状态中独特的microRNA签名。对miRBase中捕获的microRNA和新型microRNA进行计数。统计学、生物信息学和计算生物学方法被用于精炼和解释最终的microRNAs.Results列表：从215个差异表达的microRNAs（FDR < 0.01）中，97个microRNAs在早期OA组中的>= 85%的样本中的表达与晚期OA组中的中值表达相比显示出增加或减少。将该阈值增加至>= 95%，鉴定出七种microRNA：hsa-miR-335- 3 p、hsa-miR-199 a-5 p、hsa-miR-671- 3 p、hsa-miR-1260 b、hsa-miR-191- 3 p、hsa-miR-335- 5 p和hsa-miR 543。四种新的microRNA存在于>= 50%的早期OA样本中，并具有27个预测基因靶点，与来自97个microRNA的预测基因靶点的优先级设置相同，表明共同的潜在mechanism.Conclusion：对特征良好的患者队列进行测序，产生了循环miRNome的无偏分析，并确定了一个独特的11个microRNA小组，在早期放射性膝关节OA中。(C)2020作者（S）由Elsevier Ltd代表国际骨关节炎研究协会出版。
Objective: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [KellgreneLawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state.Design: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs.Results: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in >= 85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to >= 95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR543. Four novel microRNAs were present in >= 50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms.Conclusion: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.