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心力衰竭细胞外囊泡 miRNA 谱分析。

Analysis of extracellular vesicle miRNA profiles in heart failure.

机构信息

Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Pathology Department, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

J Cell Mol Med. 2020 Jul;24(13):7214-7227. doi: 10.1111/jcmm.15251. Epub 2020 Jun 2.

Abstract

Extracellular vesicles (EVs) have recently emerged as an important carrier for various genetic materials including microRNAs (miRs). Growing evidences suggested that several miRs transported by EVs were particularly involved in modulating cardiac function. However, it has remained unclear what miRs are enriched in EVs and play an important role in the pathological condition. Therefore, we established the miR expression profiles in EVs from murine normal and failing hearts and consecutively identified substantially altered miRs. In addition, we have performed bioinformatics approach to predict potential cardiac outcomes through the identification of miR targets. Conclusively, we observed approximately 63% of predicted targets were validated with previous reports. Notably, the predicted targets by this approach were often involved in both beneficial and malicious signalling pathways, which may reflect heterogeneous cellular origins of EVs in tissues. Lastly, there has been an active debate on U6 whether it is a proper control. Through further analysis of EV miR profiles, miR-676 was identified as a superior reference control due to its consistent and abundant expressions. In summary, our results contribute to identifying specific EV miRs for the potential therapeutic targets in heart failure and suggest that miR-676 as a new reference control for the EV miR studies.

摘要

细胞外囊泡 (EVs) 最近成为各种遗传物质的重要载体,包括 microRNAs (miRs)。越来越多的证据表明,EVs 中运输的几种 miR 特别参与调节心脏功能。然而,哪些 miR 在 EVs 中富集并在病理条件下发挥重要作用仍不清楚。因此,我们建立了来自正常和衰竭的小鼠心脏 EVs 的 miR 表达谱,并连续鉴定了大量改变的 miR。此外,我们通过鉴定 miR 靶标进行了生物信息学方法来预测潜在的心脏结局。最后,我们观察到大约 63%的预测靶标与以前的报告一致。值得注意的是,该方法预测的靶标通常涉及有益和恶意信号通路,这可能反映了组织中 EVs 的异质细胞起源。最后,关于 U6 是否是合适的对照存在激烈的争论。通过进一步分析 EV miR 谱,发现 miR-676 由于其一致和丰富的表达,是一种更合适的参考对照。总之,我们的研究结果有助于确定心力衰竭治疗的特定 EV miRs 作为潜在的治疗靶点,并表明 miR-676 作为 EV miR 研究的新参考对照。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/651a/7339231/80601f6019c5/JCMM-24-7214-g001.jpg

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