microRNA-23b表达异常与心脏发育缺陷相关性分析
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国家自然科学基金资助(81270298)


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

    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。

    Abstract:

    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:d12.5,d14.5,d16.5,d18.5. Differences among the later three time points (after d14.5) were significant (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 d10 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 in developmental defects of the heart.

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陈 斌,顾海涛,顾 群,刘 鸿,张石江. microRNA-23b表达异常与心脏发育缺陷相关性分析[J].南京医科大学学报(自然科学版),2015,(1):006-010-21

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  • 收稿日期:2014-05-23
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  • 在线发布日期: 2015-02-06
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