Long noncoding RNA FTX regulates cardiomyocyte apoptosis by targeting miR-29b-1-5p and Bcl2l2

Long noncoding RNA FTX regulates cardiomyocyte apoptosis by targeting miR-29b-1-5p and Bcl2l2
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长非编码RNA FTX通过靶向miR-29b-1-5p和Bcl2l2调节心肌细胞凋亡

DOI:
10.1016/j.bbrc.2017.11.030
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发表时间:
2018-01-01
影响因子:
3.1
通讯作者:
Zhang, Shu-Yang
Zhang, Shu-Yang
中科院分区:
生物学4区
文献类型:
--
作者:
Long, Bo;Li, Na;Zhang, Shu-Yang

文献摘要

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心肌细胞凋亡与心脏病的发病机制密切相关。长非编码RNA(Long Non Coding RNA,LncRNA)是一类调控基因表达并参与多种细胞过程的非编码RNA。然而,lncRNAs在心肌细胞凋亡中的作用尚不清楚。在我们的研究中,我们发现在缺血/再灌注损伤和过氧化氢处理下,lncRNA FIX的表达显著下调。FTX表达增强可抑制过氧化氢诱导的心肌细胞凋亡。研究发现,miR-29b-1-5p与FTX相互作用,调节Bcl2l2的表达。抑制miR-29b-1-5p可减轻过氧化氢诱导的心肌细胞凋亡。然后我们发现FTX作为miR-29b-1-5p的内源性海绵,调节miR-29b-1-5p的活性。结果表明,FTX通过调节miR-29b-1-5p介导的Bcl2l2的表达来调节心肌细胞的凋亡。我们的发现揭示了一个新的调控模型,它由FIX、miR-29b-1-5p和Bcl2l2组成。调控它们的水平可能成为解决心肌细胞凋亡相关心脏病的新途径。(C)2017 Elsevier Inc.保留所有权利。
Cardiomyocyte apoptosis correlates with the pathogenesis of heart disease. Long noncoding RNA (LncRNA) emerges as a class of noncoding RNAs that regulate gene expression and participate in various cellular processes. However, the role of lncRNAs in cardiomyocyte apoptosis remains to be elucidated. In our study, we found that lncRNA FIX is significantly down-regulated upon ischemia/reperfusion injury and hydrogen peroxide treatment. Enhanced expression of FTX inhibits cardiomyocyte apoptosis induced by hydrogen peroxide. miR-29b-1-5p was found to interact with FTX and regulate the expression of Bcl2l2. Inhibition of miR-29b-1-5p attenuated cardiomyocyte apoptosis upon hydrogen peroxide treatment. We then found that FTX, functions as endogenous sponge for miR-29b-1-5p and regulates the activity of miR-29b-1-5p. The results demonstrate that FTX regulates cardiomyocyte apoptosis through modulating the expression of Bcl2l2 which is mediated by miR-29b-1-5p. Our findings reveal a novel regulatory model which is composed of FIX, miR-29b-1-5p and Bcl2l2. Manipulating of their levels may become a new approach to tackling cardiomyocyte apoptosis related heart diseases. (C) 2017 Elsevier Inc. All rights reserved.