SLC35E3 identified as a target of novel‑m1061‑5p via microRNA profiling of patients with cardiovascular disease.

SLC35E3 identified as a target of novel‑m1061‑5p via microRNA profiling of patients with cardiovascular disease.
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DOI:
10.3892/mmr.2018.8498
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发表时间:
2018-04
影响因子:
3.4
通讯作者:
Huo R
Huo R
中科院分区:
医学4区
文献类型:
--
作者:
Gao F;Wang FG;Lyu RR;Xue F;Zhang J;Huo R

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MicroRNAs(MiRNA)被认为是治疗各种心血管疾病的潜在靶点。为了了解与CVD相关的miRNAs和靶基因的潜在机制,使用Illumina HiSeq 2000系统对3名CVD患者和3名对照的血液样本进行了深度测序。本研究结果显示,65个异常的hsa-miRNAs靶向2,784个可能基因,59个上调的miRNAs靶向2,401个基因,6个下调的miRNAs靶向383个基因。此外,在京都基因和基因组百科全书(KEGG)的12条途径中,共有49个基因本体论(GO)生物学过程和下调的miRNAs的靶基因得到了丰富。这些途径中的大多数都与脂肪和糖类代谢有关。其中,hsa-miR-1268b、hsa-miR-1273d、hsa-miR-3187-5p三个下调的miRNAs参与了α-亚麻酸的代谢。上调的miRNAs的靶基因在15条KEGG途径中得到了丰富,主要集中在神经退行性疾病和癌症类中。在本研究中,在CVD患者中发现了5个新的上调的miRNAs,包括m0499-5p、m0970-5p、m1042-5p、m1061-5p和m1953-5p,以及一个下调的miRNAs-m1627-5p。新奇的m1627-5p被证明靶向146个人类基因。另外,new-m1061-5p针对4个基因,包括富马酸乙酰乙酸酯水解酶结构域(含2A)、钾电压门控通道、Shaw相关亚家族、成员4、包含85C的盘绕结构域和溶质载体家族35成员E3(SLC35E3)。GO术语“参与生物过程的碳水化合物衍生运输”与SLC35E3有关。新型m1061-5p在CVD患者中可能抑制SLC35E3的表达水平,SLC35E3是核苷糖转运体E亚家族的成员,已知的是导致高尔基复合体和/或内质网中有缺陷的甘醇结合。需要进一步的研究才能理解新的miRNAs的潜在机制。New-m1061-5p可作为判断预后的指标或治疗CVD的潜在靶点。
MicroRNAs (miRNA) are considered to be potential therapeutic targets for the treatment of various cardiovascular diseases (CVDs). To understand the underlying mechanism of miRNAs and target genes associated with CVD, deep sequencing of blood samples from three patients with CVD and three controls was performed using the Illumina HiSeq 2000 system. The results of the present study revealed that 65 abnormal hsa-miRNAs targeted 2,784 putative genes in patients with CVD; 59 upregulated miRNAs targeted 2,401 genes and six downregulated miRNAs targeted 383 genes. In addition, a total of 49 Gene Ontology (GO) biological processes and were enriched, and the target genes of downregulated miRNAs were enriched in 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of these pathways are responsible for lipid and glycan metabolism. In particular, three downregulated miRNAs, hsa-miR-1268b, hsa-miR-1273d, hsa-miR-3187-5p, were involved in a-linolenic acid metabolism. The target genes of upregulated miRNAs were enriched in 15 KEGG pathways, mainly in the ‘neurodegenerative diseases and cancers’ class. In the present study five novel upregulated miRNAs, including m0499-5p, m0970-5p, m1042-5p, m1061-5p and m1953-5p, and a downregulated miRNA, novel-m1627-5p, were identified in patients with CVD. Novel-m1627-5p was demonstrated to target 146 human genes. Additionally, Novel-m1061-5p targeted four genes, including fumarylacetoacetate hydrolase domain containing 2A, potassium voltage-gated channel, Shaw-related subfamily, member 4, coiled-coil domain containing 85C and solute carrier family 35 member E3 (SLC35E3). The GO term, ‘carbohydrate derivative transport involving in biological process’, was associated with SLC35E3. Novel-m1061-5p in patients with CVD may repress the expression levels of SLC35E3, a member of the nucleoside sugar transporter subfamily E, which is known to cause defective glycol-conjugation in the Golgi complex and/or the endoplasmic reticulum. Further investigation is required to understand the underlying mechanisms of the novel miRNAs. Novel-m1061-5p may serve as a marker for prognosis or a potential target for the treatment of CVD.
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期刊: Science (New York, N.Y.)
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作者:
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发表时间: 2010-06-18
期刊: Science (New York, N.Y.)
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