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miR-181a-5p 是多发性硬化症中潜在的候选表观遗传生物标志物。

miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis.

机构信息

Department of Medical Biology, Medical Faculty, Muğla Sıtkı Koçman University, Muğla, Turkey.

Department of Nutrition and Dietetics, Health Sciences Faculty, Gaziantep University, Gaziantep, Turkey.

出版信息

Genome. 2022 Nov 1;65(11):547-561. doi: 10.1139/gen-2022-0040. Epub 2022 Sep 14.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNAs) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (, , , and was investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS),  = 27; secondary progressive MS (SPMS),  = 12) and 30 healthy controls. In silico analyses revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative real-time PCR (qPCR). was downregulated and associated with increased MS risk ( = 0.012). The other three miRNAs were upregulated and not associated with MS ( < 0.05). The area under the curve (AUC) is 0.779. In silico analyses showed that may participate in MS pathology by targeting , , , and genes in inflammation and neurodegeneration pathways. The circulatory can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and for therapeutic purpose.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的慢性炎症性疾病,其特征在于脱髓鞘和轴突变性。微小 RNA(miRNA)的异常表达在 MS 病理学中起着重要作用。在这项队列研究中,研究人员在 69 个人中研究了四种 miRNA(,,,和 的差异表达,其中包括 39 名 MS 患者(复发缓解型 MS(RRMS),=27;继发进展型 MS(SPMS),=12)和 30 名健康对照者。计算机分析揭示了特定于 miRNA 的可能基因和途径。通过定量实时 PCR(qPCR)检测外周血 miRNA 表达。下调与 MS 风险增加相关(=0.012)。其他三种 miRNA 上调,但与 MS 无关(<0.05)。曲线下面积(AUC)为 0.779。计算机分析表明,可能通过靶向炎症和神经退行性变途径中的、、和基因参与 MS 病理学。循环可以调节靶基因,从而逆转 MS 病理过程中涉及的机制,如蛋白摄取和加工、细胞增殖和存活、炎症和神经退行性变。因此,这种 miRNA 可以用作表观基因组指导的诊断工具和治疗目的。

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