Liang Dandan, Xu Xinran, Deng Fangfei, Feng Jing, Zhang Hong, Liu Ying, Zhang Yangyang, Pan Lei, Liu Yi, Zhang Dasheng, Li Jun, Liang Xingqun, Sun Yunfu, Xiao Junjie, Chen Yi-Han
Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Medical Genetics, Tongji University, Shanghai, China.
J Cell Mol Med. 2014 Sep;18(9):1830-9. doi: 10.1111/jcmm.12309. Epub 2014 Jun 1.
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.
法洛四联症（TOF）是一种复杂的先天性心脏缺陷，而微小RNA在TOF发育过程中的调控作用在很大程度上尚不明确。在此，我们探究了微小RNA在TOF中的作用。在从人类心脏组织中鉴定出的75种失调的微小RNA中，miRNA - 940是下调最为明显的一种。有趣的是，与其他心脏腔室相比，miRNA - 940在正常人类右心室流出道中表达最高。由于TOF是由第二心脏场祖细胞的增殖、迁移和/或分化改变所引起的，我们分离了Sca - 1(+)人类心肌祖细胞（hCMPC）用于miRNA - 940功能分析。miRNA - 940表达降低显著促进了hCMPC的增殖并抑制了hCMPC的迁移。我们发现JARID2是受miRNA - 940调控的一个内源性靶点。功能分析表明JARID2也影响hCMPC的增殖和迁移。因此，miRNA - 940表达降低通过靶向JARID2影响第二心脏场祖细胞的增殖和迁移，并可能导致TOF的发生。
Zotero 插件
