MicroRNA miR-27a-3p accelerates cardiac hypertrophy by targeting neuro-oncological ventral antigen 1.

MicroRNA miR-27a-3p accelerates cardiac hypertrophy by targeting neuro-oncological ventral antigen 1.
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DOI:
10.1080/21655979.2022.2054150
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发表时间:
2022-04
期刊:
影响因子:
4.9
通讯作者:
Bai Y
Bai Y
中科院分区:
生物学2区
文献类型:
--
作者:
Li D;Shen M;Deng X;Bai Y

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miRNA 是一类小非编码 RNA (ncRNA),负责靶基因的转录后调控。越来越多的证据表明 miRNA 与心脏肥大的进展有关。因此,了解这些 miRNA 如何调节心脏肥大的分子机制有助于诊断和监测疾病进展。在本研究中,为了研究miR-27a-3p的作用,我们通过用血管紧张素II(Ang II)处理H9c2心肌细胞建立了体外心脏肥大模型,并通过将Ang II长期输注给小鼠建立了体内模型。我们的实验结果表明,在心脏肥大的临床样本、动物和细胞模型中,miR-27a-3p 表达显着增加。抑制 miR-27a-3p 可减轻 Ang II 诱导的心脏肥大表型。此外,我们的工作将 NOVA1(神经肿瘤腹侧抗原 1)确定为 miR-27a-3p 的下游靶标。 miR-27a-3p 过表达降低了 NOVA1 蛋白水平和 mRNA 表达。一致地,NOVA1 沉默促进了 Ang II 诱导的心脏肥大表型。总之,这些结果表明miR-27a-3p的上调可能作为心脏肥大的诊断因素,并且miR-27a-3p的上调通过靶向NOVA1促进心脏肥大。
MiRNAs are a class of small non-coding RNAs (ncRNAs) responsible for post-transcriptional regulation of target genes. Accumulating evidence indicates that miRNAs are implicated in the progression of cardiac hypertrophy. Therefore, understanding the molecular mechanisms how these miRNAs regulate cardiac hypertrophy is useful for diagnosis and monitoring of disease progression. In this study, to investigate the effect of miR-27a-3p, we established an in vitro cardiac hypertrophy model by treating H9c2 cardiomyocytes with angiotensin II (Ang II) and an in vivo model through the chronic infusion of Ang II into mice. As revealed by our experimental results, miR-27a-3p expression was significantly increased in clinical samples, animal and cell models of cardiac hypertrophy. Inhibiting miR-27a-3p mitigated cardiac hypertrophy phenotype induced by Ang II. Additionally, our work identified NOVA1 (neuro-oncological ventral antigen 1) as a downstream target of miR-27a-3p. miR-27a-3p overexpression reduced NOVA1 protein level and mRNA expression. Consistently, NOVA1 silencing promoted cardiac hypertrophy phenotype induced by Ang II. In summary, these results suggest that the upregulation of miR-27a-3p may serve as a diagnostic factor for cardiac hypertrophy, and miR-27a-3p upregulation promotes cardiac hypertrophy by targeting NOVA1.
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