摘要
目的通过了解妊娠期糖尿病(gestational diabetes mellitus, GDM)孕妇外周血中环状核糖核酸(circular RNA, circRNA)的表达情况,为研究GDM发病机制提供科学依据。 方法运用基于前瞻性队列研究的巢式病例对照研究方法,选取2014年9月至2016年4月间在广州市妇女儿童医疗中心产前检查和分娩的1 018例孕产妇,记录产前检查信息,随访分娩结局。选取6例确诊为GDM的孕妇作为GDM组,按1∶1比例选取收集血样标本时孕周相差少于7 d、既往怀孕次数相差少于2次、既往分娩次数相同的6例正常孕妇作为对照组。通过染色体微阵列技术分析孕妇外周血中circRNA的表达情况,利用GO(http://www.geneontology.org/)、KEGG PATHWAY(http://www.genome.jp/kegg/pathway.html)、CircNet(http://circnet.mbc.nctu.edu.tw/)等数据库进行功能分析及调控网络预测。采用t检验进行数据分析。 结果与对照组比较,GDM组孕妇中差异表达倍数>2.0的circRNA有2 678个,其中1 532个circRNA为上调表达,1 146个为下调表达。功能分析发现,表达上调的circRNA富集于胰岛素响应、基因沉默调控、胰高血糖素响应及细胞衰老等生物过程;信号通路分析发现,circRNA参与胰岛素通路。分别以has_circ_0042852和has_circ_0004001为中心,预测得到可能与GDM相关的调控网络。 结论GDM孕妇外周血中circRNA含量丰富,并且参与多种生物过程、胰岛素信号通路以及可能参与GDM有关调控网络。
ObjectiveTo investigate the expression of circular RNA (circRNA) in peripheral blood of gravidas with gestational diabetes mellitus (GDM) using gene chip technology, and to provide evidence for studying pathogenesis of GDM. MethodsA prospective cohort-based nested case-control study was used to select 1 018 pregnant women who were examined and delivered in Guangzhou Women and Children's Medical Center from September 2014 to April 2016. The information of prenatal examination was recorded and the outcome of delivery was followed up. Six pregnant women diagnosed as GDM were selected as the GDM group. Six normal pregnant women who were collected blood samples by 1∶1 were selected as the control group. The difference of gestational week was less than 7 days, the number of previous pregnancies was less than 2 times, and the difference of previous delivery times as same as the control group. The expression of circRNA in maternal peripheral blood was analyzed by chromosome microarray technique, and the function and the regulation network forecast were analyzed by GO (http://www.geneontology.org/), KEGG PATHWAY (http://www.genome.jp/kegg/pathway.html) and CircNet(http://circnet.mbc.nctu.edu.tw/). t-test was used for data analysis. ResultsCompared to the normal pregnant women, 2 678 circRNAs were identified to be differentially expressed >2.0 times in GDM women, among which 1 532 were up-regulated and 1 146 were down-regulated. Functional analysis showed that the up-regulated circRNA was enriched in the biological processes of insulin response, gene silencing regulation, glucagon response and cell senescence. Signal pathway analysis showed that circRNA involved in insulin pathway. Taking has_circ_0042852 and has_circ_0004001 as center, the possible GDM-related regulatory networks were predicted. ConclusionsThe peripheral blood of GDM women is rich in circRNAs, which might involve in many biological processes, insulin signaling pathway and possibly induding GDM-related regulatory networks.
作者
陈瑞华
杨红玲
陈荣
马骏
龙燕
朱春燕
Chen Ruihua;Yang Hongling;Chen Rong;Ma Jun;Long Yan;Zhu Chunyan(School of Public Health, Guangzhou Medical University, Guangzhou 511436, China;Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China;Health Education Center of Guangzhou Panyu, Guangzhou 511400, China)
出处
《中华围产医学杂志》
CAS
CSCD
北大核心
2019年第4期255-260,共6页
Chinese Journal of Perinatal Medicine
基金
广州市科技计划项目(201707010497).
关键词
糖尿病
妊娠
RNA
基因表达谱
生物标记
Diabetes, gestational
RNA
Gene expression profiling
Biomarkers