产科抗磷脂综合征患者胎盘微RNA图谱。

IF 0.6 4区 医学 Q4 PATHOLOGY Malaysian Journal of Pathology Pub Date : 2023-12-01
M A Mohamad, A W Ahmad Asnawi, M S Suhiman, J Sathar, A R Hayati, N S Abdul Rahim, M A Masri, N Abdul Hamid, S Nurul Farihah, N Mohamad Nor, M M Nur Fariha
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引用次数: 0

摘要

当抗磷脂抗体作用于胎盘时,就会引发产科抗磷脂综合征(APS)。在怀孕期间,APS 表现出血管栓塞、炎症和滋养细胞着床受阻等特征。微小核糖核酸(microRNA)的表达被认为是导致该综合征发生的遗传因素之一。MicroRNA 在各种细胞过程(包括胎盘组织的形成)中发挥着调节基因表达的作用。因此,需要进行更多的研究来探索 APS 中胎盘 miRNA 的控制。本研究旨在分析 APS 患者胎盘组织中 miRNA 的表达。确定了其目标基因和通路的差异表达 miRNA。使用安捷伦芯片平台测量正常胎盘组织和APS患者胎盘组织的胎盘microRNA表达。使用 GeneSpring GX 软件 14.2 检测差异表达的 miRNA,并使用 TargetScan 软件绘制序列,生成预测的靶基因。然后用 PANTHER 和 REACTOME 软件对这些基因进行通路分析。利用 qPCR 验证了选定的 miRNA 及其相关基因。微阵列研究结果显示,APS 患者胎盘中有 9 个 miRNA 表达下调,21 个表达上调。3 个选定 miRNA 的定量表达与微阵列结果一致,但只有 miR-525-5p 的表达具有统计学意义。通路分析显示,差异表达的 miRNA 的靶基因参与了几种假设的信号通路,如血管内皮(VE)生长因子(VEGF)和炎症通路。VE-cadherin、ras同源物成员A(RHOA)和酪氨酸激酶受体(KIT)明显下调,而视网膜母细胞瘤基因(RET)、双特异性蛋白磷酸酶10(DUSP10)和B淋巴细胞激酶(BLK)基因则明显上调。这些初步研究结果表明,miRNAs 和新发现的相关基因参与了产科 APS 的发病机制,特别是通过改变血管相关调节因子和炎症信号级联。
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Placenta microRNA profile of patient with Obstetric Antiphospholipid Syndrome.

The onset of obstetric antiphospholipid syndrome (APS) occurs when antiphospholipid antibodies act upon the placenta. During pregnancy, APS exhibits traits such as vascular thrombosis, inflammation, and hindered trophoblast implantation. The involvement of microRNA expression has been proposed as a genetic factor contributing to the syndrome's development. MicroRNAs play a role in regulating gene expression in various cellular processes, including the formation of placental tissue. Therefore, additional research is needed to explore the control of placental miRNA in APS. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesised signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation while Retinoblastoma gene (RET), Dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) genes were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.

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来源期刊
CiteScore
3.60
自引率
5.60%
发文量
34
期刊介绍: The Malaysian Journal of Pathology is the official journal of the College of Pathologists, Academy of Medicine Malaysia. The primary purpose of The Journal is to publish the results of study and research in Pathology, especially those that have particular relevance to human disease occurring in Malaysia and other countries in this region. The term PATHOLOGY will be interpreted in its broadest sense to include Chemical Pathology, Cytology, Experimental Pathology, Forensic Pathology, Haematology, Histopathology, Immunology, Medical Microbiology and Parasitology. The Journal aims to bring under one cover publications of regional interest embracing the various sub-specialities of Pathology. It is expected that the articles published would be of value not only to pathologists, but also to medical practitioners in search of a scientific basis for the problems encountered in their practice, and to those with an interest in diseases which occur in the tropics.
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