妊娠期高血压患者胎盘组织中circRNA 表达差异及其潜在作用机制

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摘要目的基于高通量测序检测妊娠期高血压患者与健康产妇胎盘中环状RNA(circRNA)表达差异,探讨妊娠期高血压发病机制。方法选取某三甲医院2018-02至2018-12期间收治的6例患有妊娠期高血压的产妇为研究对象(M组),选择同期的6例健康产妇作为对照组(C组)。采用BWA-MEM将妊娠高血压组患者与健康对照组的胎盘组织质控后测序,使用CIRI2对circRNA鉴定,并确定circRNA来源。利用DEGseq进行circRNA差异表达分析。采用miRanda软件和该物种的miRBase序列来预测circRNA的靶标miRNA,再利用Targetscan数据库预测相应的mRNA。将差异circRNA靶基因进行GO和KEGG富集分析,并导入String在线数据库进行聚类分析,寻找处于网络核心的基因。结果两组共有31个circRNA存在差异,14个下调,17个上调,其中前5个上调circRNA分别是circRNA00809、circRNA00593、circRNA00166、circRNA00184、circRNA00028,前5个下调circRNA分别是circRNA00520、circRNA00714、circRNA02491、circRNA00841、circRNA01454。GO富集分析显示,主要富集的生物学过程为生殖过程;主要富集的细胞组分是胞外区;主要富集的分子功能是电子转移活性。KEGG通路富集中,新陈代谢方面涉及的最多。相互作用网络分析可见,NOTCH1/2处于核心位置。结论胎盘组织中31种circRNA的差异表达与妊娠期高血压相关,其可能主要通过调节物质代谢通路发挥作用,同时NOTCH1/2等基因处于调控网络中心。

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	吕俊刚
	翟莉
	刘金龙
	张琳
	王娜
	逄瑷博
	闫志风

关键词 ：妊娠期高血压, 高通量测序, circRNA, 胎盘

Abstract：Objective To detect the difference of circular RNA (circRNA) expression in placentas between patients with gestational hypertension and healthy women based on high-throughput sequencing, and to explore the pathogenesis of gestational hypertension. Methods Six pregnant women with gestational hypertension admitted to the First Medical Center of PLA General Hospital from February 2018 to December 2018 were selected as the research objects (group M), and six healthy pregnant women in the same period were selected as the control group (group C). Placental tissues from patients in group M and group C were sequenced after quality control using BWA-MEM, circRNAs were identified using CIRI2, and the source of circRNAs was determined. CircRNA differential expression analysis was performed using DEGseq. The target miRNA of circRNA was predicted by miRanda software and miRBase sequence of this species, and the corresponding mRNA was predicted by Targetscan database. GO and KEGG enrichment analysis were performed on the differentially expressed circRNA target genes, and the genes were imported into String online database for cluster analysis, and the genes at the core of the network were searched. Results There were 31 differential circRNAs in the two groups of samples, 14 down-regulated and 17 up-regulated, among which the first five up-regulated circRNAs were circRNA00809, circRNA00593, circRNA00166, circRNA00184 and circRNA00028 respectively, and the first five down-regulated circRNAs were circRNA00520, circRNA00714, circRNA02491, circRNA00841 and circRNA01454 respectively. GO enrichment analysis showed that the main biological process of enrichment was reproduction process. The main enriched cell component was extracellular region. The main enriched molecular function was electron transfer activity. Metabolism was the most involved in the enrichment of KEGG pathway. Interaction network analysis showed that NOTCH1/2 was at the core. Conclusions The differential expression of 31 circRNAs in placenta is associated with gestational hypertension, which may play a role by regulating metabolic pathways, and NOTCH1/2 and other genes are at the center of regulatory network.

Key words： gestational hypertension high-throughput sequencing circRNA placenta

收稿日期: 2023-07-17

ZTFLH:

R246.3

通讯作者: 闫志风,E-mail:yanzhifeng2002@163.com

作者简介: 吕俊刚,本科学历,副主任医师。

引用本文:

吕俊刚, 翟莉, 刘金龙, 张琳, 王娜, 逄瑷博, 闫志风. 妊娠期高血压患者胎盘组织中circRNA 表达差异及其潜在作用机制[J]. 武警医学, 2024, 35(4): 329-334. LV Jungang, ZHAI Li, LIU Jinlong, ZHANG Lin, WANG Na, PANG Aibo, YAN Zhifeng. Differential expression of circRNA in placenta of patients with gestational hypertension and its potential mechanism. Med. J. Chin. Peop. Armed Poli. Forc., 2024, 35(4): 329-334.

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http://journal08.magtechjournal.com/Jwk_wjyx/CN/ 或 http://journal08.magtechjournal.com/Jwk_wjyx/CN/Y2024/V35/I4/329

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