miRNA介导VEGF表达调控罗非鱼的低氧应答

摘要： 罗非鱼是一种适合用于低氧胁迫研究的动物模型。在低氧条件VEGF通过调控生理性和病理性血管的生成应答低氧胁迫。因此，如何精细调控VEGF表达水平对于罗非鱼的低氧耐受至关重要。研究发现，miRNA可以在转录后水平发挥调控作用，从而参与调控动物胁迫反应。据此，可以推测miRNA有望通过调控VEGF表达发挥应答低氧胁迫。 生物信息预测发现，VEGF的3'-UTR区具有miR-204的结合位点。低氧胁迫可以上调VEGF的水平，同时miR-204表达发生下调。miR-204可以作用 VEGF的3'-UTR区，且在体内干预miR-204水平可以影响VEGF水平。miR-204敲除可以影响血液内氧气的运输能力，能量代谢和抗氧化酶活性。总之， miR-204是一个内源性的VEGF表达调控因子，通过基因网络调控从而应答低氧胁迫。
关键词： 水产养殖;罗非鱼; 低氧胁迫; miR-204; VEGF。

Zhao Yan^1,， Yan Biao^1,， Zhao Jinliang^1,， Zhu Changdong^1,， Wang Zhenhua^2,*

（  1、College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306；       2、College of Information Technology, Shanghai Ocean University, Shanghai, 201306；  ）

Abstract： 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 level in 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.
Keywords： Aquaclture; Nile tilapia; Hypoxia stress; miR-204; VEGF