Overexpression of miR-135b attenuates pathological cardiac hypertrophy by targeting CACNA1C
Overexpression of miR-135b attenuates pathological cardiac hypertrophy by targeting CACNA1C
复制标题
miR-135b 的过表达通过靶向 CACNA1C 减轻病理性心脏肥大
DOI：
10.1016/j.ijcard.2018.07.016
复制
发表时间：
2018-10-15
影响因子：
3.5
通讯作者：
Yang, Baofeng
中科院分区：
文献类型：
--
作者：
Chu, Qun;Li, Anqi;Yang, Baofeng
背景：心肌肥厚是导致心力衰竭的重要因素。虽然大量的致病基因已被确定，心肌肥厚的潜在分子机制仍然知之甚少。MicroRNA是一类在转录后水平调控靶基因的非编码小RNA。L型钙通道在细胞肥大信号转导中起重要作用，CACNA 1C由L型钙通道编码。在此，我们假设过表达miR-135 b可以通过靶向CACNA 1C来减轻心肌肥厚。方法：在心肌肥厚模型中检测miR-135 b的功能。为了评价miR-135 b在心肌肥大中的作用，使用miR-135 b模拟物、miR-135 b阿戈米尔和α-MHC-miR-135 b转基因小鼠来过表达miR-135 b。结果：在病理性心肌肥厚模型中，miR-135 b的表达明显下调。在体外敲低miR-135 b后，肥大标志物基因上调，而miR-135 b的过表达减弱肥大。这些结果表明，miR-135 b可能会减弱肥大信号。我们进一步探讨了miR-135 b在肥大中的作用机制，并确定了CACNA 1C是miR-135 b的靶基因。结论：miR-135 b是心肌细胞肥大的重要调控因子。我们的研究结果可能为心肌肥厚的治疗提供一种新的策略。(c)2018 Elsevier B. V.版权所有。
Background: Cardiac hypertrophy is a serious factor underlying heart failure. Although a large number of pathogenic genes have been identified, the underlying molecular mechanisms of cardiac hypertrophy are still poorly understood. MicroRNAs are a class of small non-coding RNAs which regulate their target genes at the post-transcriptional level. L-type calcium channels play important role in hypertrophic signaling pathways, and CACNA1C is encoded by L-type calcium channels. Here, we hypothesize that the overexpression of miR-135b can attenuate hypertrophy by targeting CACNA1C.Methods: We test the functional involvement of miR-135b in cardiac hypertrophy model. In order to evaluate the effect of miR-135b in cardiac hypertrophy, miR-135b mimic, miR-135b agomir and alpha-MHC-miR-135b transgenic mice were used for the overexpression of miR-135b. Luciferase reporter assays were used to testify the binding of miR-135b to the CACNA1C 3'UTR.Results: Our results revealed that in a pathological cardiac hypertrophy model, the expression of miR-135b was clearly downregulated. Hypertrophic marker genes were upregulated after the knockdown of miR-135b in vitro, while the overexpression of miR-135b attenuated hypertrophy. These results suggested that miR-135b may weaken hypertrophic signals. We then explored the mechanism of miR-135b in hypertrophy and identified that CACNA1C was a target gene for miR-135b. The overexpression of miR-135b attenuated cardiac hypertrophy by targeting CACNA1C.Conclusions: Our studies revealed that miR-135b is a critical regulator of cardiomyocyte hypertrophy. Our findings may provide a novel strategy for the treatment of cardiac hypertrophy. (c) 2018 Elsevier B.V. All rights reserved.