miR-218 Involvement in Cardiomyocyte Hypertrophy Is Likely through Targeting REST.
miR-218 Involvement in Cardiomyocyte Hypertrophy Is Likely through Targeting REST.
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miR-218 可能通过靶向 REST 参与心肌细胞肥大
DOI：
10.3390/ijms17060848
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发表时间：
2016-05-31
影响因子：
5.6
通讯作者：
Peng LY
中科院分区：
文献类型：
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作者：
Liu JJ;Zhao CM;Li ZG;Wang YM;Miao W;Wu XJ;Wang WJ;Liu C;Wang D;Wang K;Li L;Peng LY
MicroRNA（miRNAs）已被鉴定为心肌细胞肥大的关键参与者，心肌细胞肥大与心力衰竭的显著风险相关。然而，许多microRNA在病理生理过程中的功能仍然没有得到认可。在这项研究中，我们使用体外和体内模型评估了miR-218在心肌细胞肥大中的作用。我们发现miR-218在横主动脉缩窄（TAC）小鼠模型中明显下调。miR-218的过表达足以减少肥大，而miR-218的抑制则会加重异丙肾上腺素（ISO）诱导的原代心肌细胞肥大。此外，我们确定RE 1沉默转录因子（REST）作为miR-218的新靶点;它在肥大心肌细胞和TAC模型中负调控REST的表达。这些结果表明，miR-218在心肌细胞肥大中起着至关重要的作用，可能通过靶向REST，这表明了干扰肥大的潜在候选靶标。
MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO). In addition, we identified RE1-silencing transcription factor (REST) as a novel target of miR-218; it negatively regulated the expression of REST in hypertrophic cardiomyocytes and the TAC model. These results showed that miR-218 plays a crucial role in cardiomyocyte hypertrophy, likely via targeting REST, suggesting a potential candidate target for interfering hypertrophy.