title: miRNA-directed regulation of VEGF in tilapia under hypoxia condition.
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.
authors.affiliation: College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Chang-Dong
authors.initials: CD
authors.lastname: Zhu
authors.affiliation: College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: College of Information Technology, Shanghai Ocean University, Shanghai 201306, China. Electronic address: wangzhenhua0531@126.com.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D023681:Cichlids / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000975:Antioxidants; D029941:Fish Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A
keywords: Hypoxia stress; Nile tilapia; VEGF; miR-204