miRNA-directed regulation of VEGF in tilapia under hypoxia condition.
miRNA-directed regulation of VEGF in tilapia under hypoxia condition.
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DOI：
10.1016/j.bbrc.2014.10.068
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发表时间：
2014-11
影响因子：
3.1
通讯作者：
Yan Zhao;Chang-dong Zhu;B. Yan;Jin-liang Zhao;Zhenhua Wang
中科院分区：
文献类型：
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作者：
Yan Zhao;Chang-dong Zhu;B. Yan;Jin-liang Zhao;Zhenhua Wang
尼罗河罗非鱼是耐缺氧的优秀模型。血管内皮生长因子（VEGF）在缺氧条件下生理性血管形成和病理性血管生成中起关键作用。紧密调节VEGF水平是罗非鱼低氧适应的必要条件。microRNAs（miRNAs）是转录后水平基因表达的重要调控因子，参与胁迫反应。我们推断VEGF水平可以通过miRNA调节。通过生物信息学分析，我们确定了VEGF mRNA中的一个推定的miR-204结合位点。我们发现缺氧导致VEGF水平显著上调，而miR-204水平降低。miR-204通过靶向其3′-UTR直接调节VEGF表达，并且miR-204的抑制显著增加体内VEGF水平。此外，我们发现miR-204的功能丧失会影响血液载氧能力、无氧代谢和抗氧化酶活性。总之，miR-204是VEGF表达的内源性调节因子，其参与允许在缺氧应激时快速基因程序转换的调节回路。
The Nile tilapia represents an excellent model for hypoxia tolerance. Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis under hypoxia conditions. Tight regulation of VEGF level is necessary for hypoxia adaptation in tilapia. MicroRNAs (miRNAs) function as important regulators of gene expression at the post-transcriptional level, which are usually involved in stress responses. We reasoned that VEGF level could be regulated by miRNAs. Through bioinformatics analysis, we identified a putative miR-204 binding site in the VEGF mRNA. We found that hypoxia leads to a marked up-regulation in VEGF level, but a decrease in miR-204 level. miR-204 directly regulates VEGF expression by targeting its 3′-UTR, and inhibition of miR-204 substantially increases VEGF levelin vivo. Moreover, we found that miR-204 loss of function could affect blood O2-carrying capacity, anaerobic metabolism, and antioxidant enzyme activity. Taken together, miR-204 is an endogenous regulator of VEGF expression, which participates in a regulatory circuit that allows rapid gene program transitions upon hypoxia stress.