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长链非编码 RNA uc.4 通过 TGF-β 信号通路影响细胞分化。

The long non-coding RNA uc.4 influences cell differentiation through the TGF-beta signaling pathway.

机构信息

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Cardiology, YinZhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.

出版信息

Exp Mol Med. 2018 Feb 16;50(2):e447. doi: 10.1038/emm.2017.278.

Abstract

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.

摘要

在之前的研究中,我们筛选了数千个长非编码 RNA(lncRNA),以评估它们与先天性心脏病(CHD)的潜在关系。在这项研究中,uc.4 引起了我们的注意,因为它具有高度的进化保守性,并且与 CASZ1 基因呈反义方向,CASZ1 基因对心脏发育至关重要。我们探索了 uc.4 在细胞和斑马鱼中的功能,并描述了一种潜在的作用机制。我们使用 P19 细胞来研究 uc.4 的功能。我们研究了 uc.4 过表达对斑马鱼心脏发育的影响。uc.4 的过表达通过抑制 TGF-β信号通路影响细胞分化,并抑制斑马鱼的心脏发育,导致心脏畸形。总之,我们的研究结果表明,uc.4 参与心脏发育,因此为 CHD 的治疗提供了一个潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbdb/5903826/5cb09fc430fa/emm2017278f1.jpg

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