miRNA-940 reduction contributes to human Tetralogy of Fallot development.

miRNA-940 reduction contributes to human Tetralogy of Fallot development.
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miRNA-940的减少有助于人类法洛四联症的发展

DOI:
10.1111/jcmm.12309
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发表时间:
2014-09
影响因子:
5.3
通讯作者:
Chen YH
Chen YH
中科院分区:
医学2区
文献类型:
--
作者:
Liang D;Xu X;Deng F;Feng J;Zhang H;Liu Y;Zhang Y;Pan L;Liu Y;Zhang D;Li J;Liang X;Sun Y;Xiao J;Chen YH

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法洛四联症(Tetralogy of Fallot,TOF)是一种复杂的先天性心脏病,其发生发展过程中microRNAs的调控机制尚不清楚。在此,我们探讨了miRNA在TOF中的作用。在75个从人类心脏组织中鉴定的失调的miRNA中,miRNA-940是下调最多的一个。有趣的是,与其他心室相比,miRNA-940在正常人右心室流出道中表达最高。由于TOF是由次级心脏区域的祖细胞的增殖、迁移和/或分化改变引起的,我们分离了Sca-1+人心肌细胞祖细胞(hCMPC)用于miRNA-940功能分析。miRNA-940减少显著促进hCMPCs增殖并抑制hCMPCs迁移。我们发现JARID 2是由miRNA-940调控的内源性靶点。功能分析表明,JARID 2也影响hCMPCs的增殖和迁移。因此,减少的miRNA-940通过靶向JARID 2影响次级心脏区域的祖细胞的增殖和迁移,并可能导致TOF的发展。
Tetralogy of Fallot (TOF) is a complex congenital heart defect and the microRNAs regulation in TOF development is largely unknown. Herein, we explored the role of miRNAs in TOF. Among 75 dysregulated miRNAs identified from human heart tissues, miRNA-940 was the most down-regulated one. Interestingly, miRNA-940 was most highly expressed in normal human right ventricular out-flow tract comparing to other heart chambers. As TOF is caused by altered proliferation, migration and/or differentiation of the progenitor cells of the secondary heart field, we isolated Sca-1+ human cardiomyocyte progenitor cells (hCMPC) for miRNA-940 function analysis. miRNA-940 reduction significantly promoted hCMPCs proliferation and inhibited hCMPCs migration. We found that JARID2 is an endogenous target regulated by miRNA-940. Functional analyses showed that JARID2 also affected hCMPCs proliferation and migration. Thus, decreased miRNA-940 affects the proliferation and migration of the progenitor cells of the secondary heart field by targeting JARID2 and potentially leads to TOF development.
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发表时间: 2010-03-11
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