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MicroRNA-150 通过下调 c-myb 基因加重 H2O2 诱导的心肌细胞损伤。

MicroRNA-150 aggravates H2O2-induced cardiac myocyte injury by down-regulating c-myb gene.

机构信息

Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):734-41. doi: 10.1093/abbs/gmt067. Epub 2013 Jul 3.

DOI:10.1093/abbs/gmt067
PMID:23824072
Abstract

MicroRNAs (miRNAs) are one class of non-coding RNAs that play an important role in post-transcriptional regulation via the degradation or translational inhibition of their target genes. MicroRNA-150 (miR-150) plays a vital role in regulating the development of B and T lymphocytes. Although the dysregulation of miR-150 was confirmed in human myocardial infarction, little is known regarding the biological functions of miR-150 in response to reactive oxygen species (ROS)-mediated gene regulation in cardiac myocytes. Using quantitative real-time reverse transcription-polymerase chain reaction, we demonstrated that the level of miR-150 was up-regulated in cardiac myocytes after treatment with hydrogen peroxide (H2O2). To identify the potential roles of miR-150 in H2O2-mediated gene regulation, we modulated expression of miR-150 using miR-150 inhibitor and miR-150 mimics. Results showed that silencing expression of miR-150 decreased H2O2-induced cardiac cell death and apoptosis. In lymphocytes, c-myb was a direct target of miR-150. In cardiac myocytes, we found that c-myb was also involved in miR-150-mediated H2O2-induced cardiac cell death. These results suggested that miR-150 participates in H2O2-mediated gene regulation and functional modulation in cardiac myocytes. MiR-150 may play an essential role in heart diseases related to ROS, such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.

摘要

微小 RNA(miRNA)是一类非编码 RNA,通过降解或翻译抑制其靶基因,在转录后调控中发挥重要作用。miRNA-150(miR-150)在调节 B 和 T 淋巴细胞发育中起着至关重要的作用。尽管已经证实 miR-150 在人类心肌梗死中失调,但关于 miR-150 在心脏肌细胞中对活性氧(ROS)介导的基因调节的生物学功能知之甚少。通过定量实时逆转录聚合酶链反应,我们证明了心脏肌细胞在过氧化氢(H2O2)处理后 miR-150 的水平上调。为了确定 miR-150 在 H2O2 介导的基因调节中的潜在作用,我们使用 miR-150 抑制剂和 miR-150 模拟物调节 miR-150 的表达。结果表明,沉默 miR-150 的表达可降低 H2O2 诱导的心脏细胞死亡和凋亡。在淋巴细胞中,c-myb 是 miR-150 的直接靶标。在心脏肌细胞中,我们发现 c-myb 也参与了 miR-150 介导的 H2O2 诱导的心脏细胞死亡。这些结果表明,miR-150 参与了 H2O2 介导的心脏肌细胞基因调节和功能调节。miR-150 可能在与 ROS 相关的心脏疾病中发挥重要作用,如心脏肥大、心力衰竭、心肌梗死和心肌缺血/再灌注损伤。

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