He Yujing, Wu Na
Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Medical Service Quality, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Diabetes Metab Syndr Obes. 2023 Mar 7;16:619-628. doi: 10.2147/DMSO.S400283. eCollection 2023.
To study the characteristics of selective polyadenylation (APA) in gestational diabetes mellitus (GDM) by poly(A) site sequencing and to explore the role of APA process in the pathogenesis of GDM.
Three pregnant women diagnosed as GDM in our hospital were randomly selected as the GDM group, and three healthy pregnant women at the same time as the control group. The placental tissues of two groups of pregnant women after delivery were collected for high-throughput transcriptome sequencing (RNA-seq) and poly(A) site sequencing (PAS-seq) to screen differentially expressed genes and variable 3'UTR genes in GDM. Gene Ontology (GO) analysis and pathway analysis were used to analyze the functional classification and pathway of differential genes, and preliminarily explore the susceptible genes in GDM.
Compared with the control group, there were 202 TTS loci in the GDM group, including 103 genes with shortened TTS loci and 99 genes with delayed TTS loci. There were 57 genes with significant difference in TTS (P<0.05). Subsequently, we found that VCPIP1 and LGR4 were differentially expressed in RNA-seq. The genes in advance of TTS locus were enriched in biological processes such as cell development, protein transport and phosphorylation, signal transduction, etc. Delayed TTS genes are enriched in biological processes such as transcriptional regulation, cell migration and cycle, DNA repair and damage.
The abnormality of APA process may be involved in the occurrence and development of GDM. The genes with significantly different changes in TTS locus may become biomarkers or predictors for GDM to assess the incidence, disease progression and disease severity, and may also become potential targets for GDM treatment.
通过聚腺苷酸化（poly(A)）位点测序研究妊娠期糖尿病（GDM）中选择性聚腺苷酸化（APA）的特征，并探讨APA过程在GDM发病机制中的作用。
随机选取我院诊断为GDM的3例孕妇作为GDM组，同期选取3例健康孕妇作为对照组。收集两组孕妇产后的胎盘组织进行高通量转录组测序（RNA-seq）和聚腺苷酸化（poly(A)）位点测序（PAS-seq），以筛选GDM中差异表达基因和可变3'非翻译区（UTR）基因。采用基因本体论（GO）分析和通路分析对差异基因进行功能分类和通路分析，初步探索GDM中的易感基因。
与对照组相比，GDM组有202个转录终止位点（TTS）位点，其中103个基因的TTS位点缩短，99个基因的TTS位点延迟。有57个基因的TTS有显著差异（P<0.05）。随后，我们发现VCPIP1和LGR4在RNA-seq中差异表达。TTS位点提前的基因富集于细胞发育、蛋白质转运和磷酸化、信号转导等生物学过程。TTS延迟的基因富集于转录调控、细胞迁移和周期、DNA修复和损伤等生物学过程。
APA过程异常可能参与GDM的发生发展。TTS位点变化显著的基因可能成为评估GDM发病率、疾病进展和疾病严重程度的生物标志物或预测指标，也可能成为GDM治疗的潜在靶点。
