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研究 epi-miRNome:使用转染实验鉴定 epi-miRNAs。

Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments.

机构信息

Department of Physics & INFN, University of Torino, 10125, Torino, Italy.

Molecular Biotechnology Center (MBC), 10126, Torino, Italy.

出版信息

Epigenomics. 2019 Nov;11(14):1581-1599. doi: 10.2217/epi-2019-0050. Epub 2019 Nov 6.

Abstract

Growing evidence shows a strong interplay between post-transcriptional regulation, mediated by miRNAs (miRs) and epigenetic regulation. Nevertheless, the number of experimentally validated miRs (called epi-miRs) involved in these regulatory circuitries is still very small. We propose a pipeline to prioritize candidate epi-miRs and to identify potential epigenetic interactors of any given miR starting from miR transfection experiment datasets. We identified 34 candidate epi-miRs: 19 of them are known epi-miRs, while 15 are new. Moreover, using an in-house generated gene expression dataset, we experimentally proved that a component of the polycomb-repressive complex 2, the histone methyltransferase enhancer of zeste homolog 2 (EZH2), interacts with miR-214, a well-known prometastatic miR in melanoma and breast cancer, highlighting a miR-214-EZH2 regulatory axis potentially relevant in tumor progression.

摘要

越来越多的证据表明,miRNAs(miRs)介导的转录后调控与表观遗传调控之间存在着强烈的相互作用。然而,在这些调控回路中,经过实验验证的 miRNAs(称为 epi-miRs)的数量仍然非常少。我们提出了一种从 miR 转染实验数据集中优先考虑候选 epi-miRs 并识别任何给定 miR 的潜在表观遗传相互作用因子的管道。我们鉴定了 34 个候选 epi-miRs:其中 19 个是已知的 epi-miRs,而 15 个是新的。此外,使用内部生成的基因表达数据集,我们通过实验证明,多梳抑制复合物 2 的一个组成部分,组蛋白甲基转移酶增强子的 zeste 同源物 2(EZH2),与 miR-214 相互作用,miR-214 是黑色素瘤和乳腺癌中一种众所周知的促转移 miR,突出了 miR-214-EZH2 调节轴在肿瘤进展中可能具有相关性。

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