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空气污染暴露诱导先天性缺陷的 microRNA 特征。

MicroRNA signature of air pollution exposure-induced congenital defects.

机构信息

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Orthopedic Surgery, The General Hospital of Xingtai Mining Industry Bloc., Orthopaedic Hospital of Xingtai, Xingtai, Hebei, China.

出版信息

J Cell Physiol. 2019 Aug;234(10):17896-17904. doi: 10.1002/jcp.28422. Epub 2019 Mar 18.

DOI:10.1002/jcp.28422
PMID:30883755
Abstract

Air pollution exposure has been increasing extensively and there are evidence suggesting that exposure to air pollution during pregnancy can lead to congenital defects in the offspring. Recent findings suggested that microRNAs (miRNAs) might play important roles in the pathogenesis of developmental defects. However, the miRNAs profile pattern in the air pollution-exposed embryos remains unknown. RNA sequencing was performed to determine the differentially expressed miRNAs in the rat embryos (gestation day 9) with or without air pollution exposure. The potential functions and the associated mechanisms of these differentially expressed miRNAs were determined using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The regulatory networks of mRNA-miRNA interactions were also reconstructed. As compared with the control group, a total of 291 miRNAs were differentially expressed in the rat embryos from the air pollution-exposed group, in which 204 and 87 miRNAs were significantly downregulated and upregulated, respectively. These miRNAs were predicted to deregulate mitotic spindle organization, cellular respiration, glycolate metabolism, and proteasome. Extensive regulation of target genes by miR-346, miR-504, miR-214-3p and miR-1224 was also predicted. Our results suggested that miRNAs may play crucial roles in the pathogenesis of air pollution-induced congenital spinal defects through deregulating multiple biological processes.

摘要

空气污染暴露广泛增加,有证据表明,怀孕期间暴露于空气污染会导致后代出现先天性缺陷。最近的研究结果表明,microRNAs(miRNAs)可能在发育缺陷的发病机制中发挥重要作用。然而,暴露于空气污染的胚胎中的 miRNAs 谱模式仍不清楚。我们进行了 RNA 测序,以确定有或没有空气污染暴露的大鼠胚胎(妊娠第 9 天)中差异表达的 miRNAs。使用京都基因与基因组百科全书(KEGG)途径和基因本体论(GO)分析确定这些差异表达 miRNAs 的潜在功能和相关机制。还重建了 mRNA-miRNA 相互作用的调控网络。与对照组相比,来自空气污染暴露组的大鼠胚胎中共有 291 个 miRNAs 差异表达,其中 204 个和 87 个 miRNAs 分别显著下调和上调。这些 miRNAs 被预测会使有丝分裂纺锤体组织、细胞呼吸、乙醛酸代谢和蛋白酶体失调。miR-346、miR-504、miR-214-3p 和 miR-1224 对靶基因的广泛调控也被预测到了。我们的结果表明,miRNAs 可能通过调节多个生物学过程,在空气污染引起的先天性脊柱缺陷发病机制中发挥关键作用。

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