High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: identification of potential weight loss biomarkers.

High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: identification of potential weight loss biomarkers.
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DOI:
10.1371/journal.pone.0054319
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Martínez JA
Martínez JA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Milagro FI;Miranda J;Portillo MP;Fernandez-Quintela A;Campión J;Martínez JA

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microRNAs(miRNAs)在能量代谢和机体组成稳态方面的研究越来越多。事实上,在不同的肥胖症条件下的miRNA表达的定量分析可能有助于了解参与体重控制的密切机制,并找到新的生物标志物与诊断或预后价值的肥胖管理。本研究的目的是寻找血细胞中的miRNAs,其表达可用作体重减轻的预后生物标志物。在一项减肥试验中,从参与者中选择了10名白人肥胖妇女,该试验包括能量限制治疗。当体重减轻<初始体重的5%时(无反应者)被认为是不成功的,而当>5%时(反应者)被认为是成功的。在基线时,用SOLiD v4对从外周血单核细胞(PBMC)分离的总miRNA进行测序。通过RT-PCR验证miRNA测序数据。在应答者和非应答者之间发现了几种miRNA的差异基线表达。在无应答者组中,两种miRNA上调(mir-935和mir-4772),另外三种下调(mir-223、mir-224和mir-376 b)。mir-935和mir-4772都显示出与体重减轻的程度相关,尽管其他转录物(mir-874、mir-199 b、mir-766、mir-589和mir-148 b)的表达也与体重减轻相关。本研究通过测定PBMC的miRNA转录组,解决了在寻找肥胖的miRNA表达生物标志物中使用高通量测序技术。不同miRNA的基础表达,特别是mir-935和mir-4772,可能是预后生物标志物,并可能预测对低热量饮食的反应。
MicroRNAs (miRNAs) are being increasingly studied in relation to energy metabolism and body composition homeostasis. Indeed, the quantitative analysis of miRNAs expression in different adiposity conditions may contribute to understand the intimate mechanisms participating in body weight control and to find new biomarkers with diagnostic or prognostic value in obesity management. The aim of this study was the search for miRNAs in blood cells whose expression could be used as prognostic biomarkers of weight loss. Ten Caucasian obese women were selected among the participants in a weight-loss trial that consisted in following an energy-restricted treatment. Weight loss was considered unsuccessful when <5% of initial body weight (non-responders) and successful when >5% (responders). At baseline, total miRNA isolated from peripheral blood mononuclear cells (PBMC) was sequenced with SOLiD v4. The miRNA sequencing data were validated by RT-PCR. Differential baseline expression of several miRNAs was found between responders and non-responders. Two miRNAs were up-regulated in the non-responder group (mir-935 and mir-4772) and three others were down-regulated (mir-223, mir-224 and mir-376b). Both mir-935 and mir-4772 showed relevant associations with the magnitude of weight loss, although the expression of other transcripts (mir-874, mir-199b, mir-766, mir-589 and mir-148b) also correlated with weight loss. This research addresses the use of high-throughput sequencing technologies in the search for miRNA expression biomarkers in obesity, by determining the miRNA transcriptome of PBMC. Basal expression of different miRNAs, particularly mir-935 and mir-4772, could be prognostic biomarkers and may forecast the response to a hypocaloric diet.
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