Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2024-06-13 DOI:10.1186/s40246-024-00625-5

Anelisa Gollo Dantas, Beatriz Carvalho Nunes, Natália Nunes, Pedro Galante, Paula Fontes Asprino, Vanessa Kiyomi Ota, Maria Isabel Melaragno

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引用次数: 0

Abstract

Background: The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes.

Results: In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls.

Conclusions: Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.

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22q11.2缺失综合征患者的 miRNAs 下一代测序分析表明，miR-185-5p 的表达发生了改变。

背景：22q11.2 缺失综合征（22q11.2DS）是一种微缺失综合征，尽管大多数患者表现为典型的 3 Mb 微缺失，通常影响相同的约 106 个基因，但其表型表现却千差万别。受这种缺失影响的基因之一是 DGCR8，它在 miRNA 生物发生过程中起着至关重要的作用。因此，由于这种微缺失导致的 DGCR8 的单倍性不足会改变参与一系列生物过程的多个 miRNA 的表达调控：在这项研究中，我们使用新一代测序技术评估了12名典型22q11DS患者外周血中的miRNAs谱，并与12名健康的匹配对照进行了比较。我们使用 DESeq2 软件包进行差异基因表达分析，并使用 DIANA-miTED 数据集验证差异表达的 miRNA 在其他组织中的表达情况。我们利用 miRWalk 预测了差异表达 miRNA 的靶基因。在这里，我们描述了与对照组相比，患者体内两种不同表达的 miRNA：位于 22q11.2 区域外的 hsa-miR-1304-3p 在患者体内上调，而位于 22q11.2 区域内的 hsa-miR-185-5p 则出现下调。hsa-miR-1304-3p在血液中的表达量较低，因此还需要更多的验证，尽管使用敏感的技术使我们能够确定患者与对照组之间的表达差异：因此，miR-185-5p的低表达可能与22q11.2缺失和DGCR8单倍体缺陷有关，导致22q11.2DS患者的表型后果，而hsa-miR-1304-3p的高表达可能与巴西人口的异质性背景导致的个体基因组差异有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.