MiRNA在早产胎盘中差异表达及其分子机制的研究

Preterm birth is the leading cause of newborn deaths. The cause of preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging proposition. MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. 30% of human genes regulated by miRNA.The preliminary work has been analysis of 32 cases of the preterm birth and normal placenta by using Human miRNA Microarrays and we found that top 4 of up-regulated preterm birth regulated transcripts in placenta are hsa-miR-612、hsa-miR-374a-5p、hsa-miR-302C-5p and hsa-miR-4754. So we Search for predicted miRNA targets by TargetScan and The results of the applied text mining tool indicates an involvement of preterm birth-sensitive genes in the cAMP-Mitochondria pathway.Furthermore, preterm birth may inhibit Ca2+ and mitochondria activity by decreasing level of cAMP that in turn activate CREB. Decrypt the incidence of preterm birth and mitochondrial function and calcium metabolism limited contact and the prevention of premature diagnosis has important clinical significance.

早产是导致新生儿死亡的首要原因。目前尚缺乏预防早产的有效手段，且仍有50%以上的早产其病因不明（自发性早产）。因此明确自发性早产的原因，解析人类分娩启动机制是寻找防治早产的有效途径。microRNA（miRNA），是近年来新发现的内源性小分子非编码单链RNA，人类30%的基因受miRNA的调控。本课题的前期工作利用芯片对32例自发性早产和正常分娩者的胎盘组织进行全基因组miRNA表达分析，筛选出具有表达差异且有一定生物学意义的4个miRNAs。预测miRNA靶基因发现以上4个miRNAs片段对人体的钙离子变化以及线粒体功能可能存在作用。通过对血钙浓度的调查发现，自发性早产孕妇血钙指数明显高于正常分娩者，且患者体内调节 PGC-1α的因子CREB以及与线粒体生成密切相关的因子TFBM有受到抑制的迹象。解密自发性早产的发病与线粒体功能以及钙代谢的联系对自发性早产的预防具有重要的临床意义。

早产是导致新生儿死亡的首要原因。目前尚缺乏预防早产的有效手段，且仍有50%以上的早产其病因不明（自发性早产）。因此明确自发性早产的原因，解析人类分娩启动机制是寻找 防治早产的有效途径。microRNA（miRNA），是近年来新发现的内源性小分子非编码单链RNA， 人类30%的基因受miRNA的调控。本课题的前期工作利用芯片对32例自发性早产和正常分娩者的胎盘组织进行全基因组miRNA表达分析，筛选出具有表达差异且有一定生物学意义的4个miRNAs，它们分别是hsa-miR-612、hsa-miR-374a-5p、hsa-miR- 302C-5p和 hsa-miR-4754。预测miRNA靶基因发现以上4个miRNAs片段对人体的钙离子变化以及线粒体功能可能存在作用。通过对100例自发性早产和正常分娩者的胎盘组织GDNF、CACNA1I、CREB、TFBM的基因水平以及蛋白水平进行测定以及早产患者胎盘中线粒体呼吸链复合物活性（复合物I、IV）的测定，证实了自发性早产与线粒体功能的关系。对自发性早产的预防具有一定的临床意义。