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马来西亚妊娠期糖尿病患者血清循环 MicroRNAs 水平分析。

Analysis of serum circulating MicroRNAs level in Malaysian patients with gestational diabetes mellitus.

机构信息

The Pharmacogenomics Laboratory, Department of Pharmacology, Universiti Malaya, Kuala Lumpur, Malaysia.

Department of Bioscience, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Kuala Lumpur, Malaysia.

出版信息

Sci Rep. 2022 Nov 24;12(1):20295. doi: 10.1038/s41598-022-23816-3.

Abstract

Gestational diabetes mellitus (GDM) is a severe global issue that requires immediate attention. MicroRNA expression abnormalities are possibly disease-specific and may contribute to GDM pathological processes. To date, there is limited data on miRNA profiling in GDM, especially that involves a longitudinal study. Here, we performed miRNA expression profiling in the entire duration of pregnancy (during pregnancy until parturition and postpartum) using a miRNA- polymerase chain reaction array (miRNA-PCRArray) and in-silico analysis to identify unique miRNAs expression and their anticipated target genes in Malay maternal serum. MiRNA expression levels and their unique potential as biomarkers were explored in this work. In GDM patients, the expression levels of hsa-miR-193a, hsa-miR-21, hsa-miR-23a, and hsa-miR-361 were significantly increased, but miR-130a was significantly downregulated. The area under the curve (AUC) and receiver operating characteristic (ROC) curve study demonstrated that hsa-miR-193a (AUC = 0.89060 ± 04,470, P = 0.0001), hsa-miR-21 (AUC = 0.89500 ± 04,411, P = 0.0001), and miR-130a (AUC = 0.6939 ± 0.05845, P = 0.0025) had potential biomarker features in GDM. In-silico analysis also revealed that KLF (Kruppel-Like family of transcription factor), ZNF25 (Zinc finger protein 25), AFF4 (ALF transcription elongation factor 4), C1orf143 (long intergenic non-protein coding RNA 2869), SRSF2 (serine and arginine rich splicing factor 2), and ZNF655 (Zinc finger protein 655) were prominent genes targeted by the common nodes of miR23a, miR130, miR193a, miR21, and miR361.Our findings suggest that circulating microRNAs in the first trimester has the potential for GDM screening in the Malay population.

摘要

妊娠期糖尿病(GDM)是一个严重的全球性问题,需要立即引起重视。微小 RNA 表达异常可能具有疾病特异性,并可能导致 GDM 病理过程。迄今为止,关于 GDM 中的 miRNA 分析的资料有限,特别是涉及纵向研究的资料。在这里,我们使用 miRNA-聚合酶链反应阵列(miRNA-PCRArray)和计算机分析,在整个孕期(妊娠期间直至分娩和产后)进行 miRNA 表达谱分析,以鉴定马来族产妇血清中独特的 miRNA 表达及其预期的靶基因。本研究探讨了 miRNA 表达水平及其作为生物标志物的独特潜力。在 GDM 患者中,hsa-miR-193a、hsa-miR-21、hsa-miR-23a 和 hsa-miR-361 的表达水平显著升高,但 miR-130a 显著下调。曲线下面积(AUC)和接收器操作特征(ROC)曲线研究表明,hsa-miR-193a(AUC=0.89060±04,470,P=0.0001)、hsa-miR-21(AUC=0.89500±04,411,P=0.0001)和 miR-130a(AUC=0.6939±0.05845,P=0.0025)在 GDM 中具有潜在的生物标志物特征。计算机分析还显示,KLF(转录因子 Kruppel-like 家族)、ZNF25(锌指蛋白 25)、AFF4(转录延伸因子 4)、C1orf143(长基因间非蛋白编码 RNA 2869)、SRSF2(丝氨酸/精氨酸丰富剪接因子 2)和 ZNF655(锌指蛋白 655)是 miR23a、miR130、miR193a、miR21 和 miR361 的共同节点靶向的显著基因。我们的研究结果表明,在马来人群中,第一孕期循环 microRNAs 具有 GDM 筛查的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f84/9700700/c2353e65018d/41598_2022_23816_Fig1_HTML.jpg

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