microRNA-23b表达异常与心脏发育缺陷相关性分析

Correlation analysis of abnormal miR-23b expression and cardiac developmental defects

目的:探讨microRNA-23b(miR-23b)表达异常与心脏发育缺陷的关系。方法 :收集人胚胎心肌组织和发育中的小鼠胚胎心肌组织,0.9%二甲亚砜(dimethyl sulfoxide,DMSO)诱导P19细胞定向分化为心肌细胞,定量PCR检测人胚胎心肌组织、小鼠胚胎心肌组织和P19细胞分化过程中miR-23b的表达特点,运用在线数据库对miR-23b进行生物信息学分析,分析其可能的靶基因以及涉及的信号通路,综合分析miR-23b表达异常与心脏发育缺陷的关系。结果:miR-23b在孕早期人室间隔缺损(ventricular septal defect,VSD)胚胎心肌组织中上调4.4倍,在孕中期VSD组下调3.5倍;小鼠胚胎发育d12.5、d14.5、d16.5、d18.5的4个时间点miR-23b的表达量逐渐增高,d14.5后各组间差异具有显著性(P<0.05);P19细胞定向分化过程中miR-23b的表达量逐渐下降,d4后各组间有显著差异(P<0.05);生物信息学分析提示miR-23b可能涉及转化生长因子β(TGF-β)、Notch、Wnt信号通路。结论 :miR-23b表达异常可能通过影响心肌细胞的增殖、凋亡、迁移、分化等细胞功能,导致心脏发育缺陷。

Objective：To investigate the relationship between miR-23b expression abnormalities and developmental defects of the heart. Methods：Human and developing mouse embryo myocardial tissues were collected. P19 cells,induced to differentiating into cardiomyocytes with 0.9% dimethyl sulfoxide （DMSO）,were collected at day 0,4,6,10. MiR-23b expression level of the mentioned tissues or cells was then detected. Online databases were used to predict target genes of miR-23b and the signaling pathways that the target genes may be involved in,thus to comprehensively analyze the relationship between miR-23b expression abnormalities and developmental defects of the heart. Results： For human embryos of first and second trimester of gestation,miR-23b expression was upregulated 4.4 times and downregulated 3.5 times,respectively,in the VSD （ventricular septal defect） group,compared with the normal control group. For mouse embryos,expression of miR-23b increased gradually at the four time points：dl2.5,dl4.5,dl6.5,dl8.5. Differences among the later three time points（after d14.5） were signiflcant（P 〈 0.05）. During differentiating into cardiomyocytes,P19 cells showed a descending trend in miR-23b expression. Differences between d4 and d6 or d6 and dl0 were significant（P 〈 0.05）. Bioinformatics about miR-23b suggests that it may be involved in TGF-β,Notch,Wnt signaling pathways. Conclusion：MiR-23b expression abnormalities may influence proliferation,apoptosis,migration and differentiation of cardiomyocytes and thus result indevelopmental defects of the heart.