Sources of individual variability: miRNAs that predispose to neuropathic pain identified using genome-wide sequencing.
Sources of individual variability: miRNAs that predispose to neuropathic pain identified using genome-wide sequencing.
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DOI：
10.1186/1744-8069-10-22
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发表时间：
2014-03-19
期刊：
影响因子：
3.3
通讯作者：
Devor M
中科院分区：
文献类型：
--
作者：
Bali KK;Hackenberg M;Lubin A;Kuner R;Devor M
我们开展了一项全基因组研究，使用microRNA测序(miRNA-seq)，旨在识别初级感觉神经元中与神经病理性疼痛相关的miRNAs。这种扫描通常会产生一长串受神经损伤调控的转录本，但不一定与疼痛有关。为了克服这一点，我们尝试了一种新的搜索策略：鉴定在大鼠品系中由神经损伤差异调控的转录本，除了不同的疼痛表型非常相似。于脊髓神经结扎术(SNL)后3天切取L4、5背根神经节(DRG)，提取小RNA并测序。我们鉴定了284种成熟的miRNA在大鼠DRG中表达，其中包括几个以前没有报道的物种，以及3340个独特的小RNA序列。在两个大鼠品系中，miRNA的基线表达几乎相同，与它们共同的遗传背景一致。在这两个品系中，许多miRNAs在SNL之后名义上上调或下调，但不同品系的变化是相似的。只有3个miRNAs表达水平较高(RNO-miR-30d-5p、RNO-miR-125b-5p)或表达水平中等(RNO-miR-379-5p)。这使它们成为神经病理性疼痛的新的PNS决定因素的主要候选者。前两个是已知的与神经病理性疼痛表型密切相关的基因产物--肿瘤坏死因子、脑源性神经营养因子和信号转导蛋白3表达的miRNA调节因子。少数非miRNA、小非编码RNA(SncRNAs)也受到差异调控。尽管我们的搜索策略覆盖了整个基因组，但我们的搜索策略产生了一个非常短的神经病理性疼痛相关miRNAs列表。由于这3个基因中有2个是重要的伤害感受性化合物的有效调节者，它们很可能有助于基因表达变化的协调，这些基因表达变化决定了疼痛表型的个体差异。需要进一步的研究来确定这些miRNAs的其他一些已知或预测的基因靶标，或者差异调控的非miRNASncRNAs是否也起到了作用。
We carried out a genome-wide study, using microRNA sequencing (miRNA-seq), aimed at identifying miRNAs in primary sensory neurons that are associated with neuropathic pain. Such scans usually yield long lists of transcripts regulated by nerve injury, but not necessarily related to pain. To overcome this we tried a novel search strategy: identification of transcripts regulated differentially by nerve injury in rat lines very similar except for a contrasting pain phenotype. Dorsal root ganglia (DRGs) L4 and 5 in the two lines were excised 3 days after spinal nerve ligation surgery (SNL) and small RNAs were extracted and sequenced. We identified 284 mature miRNA species expressed in rat DRGs, including several not previously reported, and 3340 unique small RNA sequences. Baseline expression of miRNA was nearly identical in the two rat lines, consistent with their shared genetic background. In both lines many miRNAs were nominally up- or down-regulated following SNL, but the change was similar across lines. Only 3 miRNAs that were expressed abundantly (rno-miR-30d-5p, rno-miR-125b-5p) or at moderate levels (rno-miR-379-5p) were differentially regulated. This makes them prime candidates as novel PNS determinants of neuropathic pain. The first two are known miRNA regulators of the expression of Tnf, Bdnf and Stat3, gene products intimately associated with neuropathic pain phenotype. A few non-miRNA, small noncoding RNAs (sncRNAs) were also differentially regulated. Despite its genome-wide coverage, our search strategy yielded a remarkably short list of neuropathic pain-related miRNAs. As 2 of the 3 are validated regulators of important pro-nociceptive compounds, it is likely that they contribute to the orchestration of gene expression changes that determine individual variability in pain phenotype. Further research is required to determine whether some of the other known or predicted gene targets of these miRNAs, or of the differentially regulated non-miRNA sncRNAs, also contribute.
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影响因子：
11.1
作者：
Bali, Kiran Kumar;Selvaraj, Deepitha;Satagopam, Venkata P.;Lu, Jianning;Schneider, Reinhard;Kuner, Rohini
通讯作者：
Kuner, Rohini
影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
通讯作者：
Walichiewicz, J
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
3.7
作者：
Devor, Marshal
通讯作者：
Devor, Marshal
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S