title: MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis.
abstract: OBJECTIVE
  MicroRNA-10 (miR-10) was originally shown to regulate angiogenesis by directly modulating the levels of membrane-bound fms-related tyrosine kinase 1 (mflt1) and its soluble splice isoform sflt1 post-transcriptionally in zebrafish. Given that flt1 knockdown incompletely rescues the angiogenic phenotypes in miR-10 morphants, flt1 is unlikely to be the only important target of miR-10 in endothelial cells (ECs). It will be interesting to investigate new mechanism responsible for angiogenic defect induced by miR-10 knockdown.
  
  
  RESULTS
  Firstly, we demonstrated that miR-10a and miR-10b (miR-10a/10b) were highly enriched in embryonic zebrafish ECs using deep sequencing, Taqman polymerase chain reaction, and in situ hybridisation. Subsequently, we proved that loss of miR-10a/10b impaired blood vessel outgrowth through regulating tip cell behaviours. Mib1 was identified as a potential direct target of miR-10a/10b through in silicon analysis and in vitro luciferase sensor assay. In vivo reporter assay in zebrafish embryos confirmed the binding of miR-10 with 3'-UTR of zebrafish mib1. Furthermore, inhibition of mib1 and Notch signaling rescued the angiogenic defects in miR-10-deficient zebrafish embryos. In addition, we provided evidences that miR-10 regulates human ECs behaviour through targeting Mib1 as well.
  
  
  CONCLUSIONS
  Taken together, these results indicate that miR-10 regulates the angiogenic behaviour in a Notch-dependent manner by directly targeting mib1.
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Chang Chun
authors.initials: CC
authors.lastname: Ling
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Medical College, Nantong University, Nantong, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Qi
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: You
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Medical College, Nantong University, Nantong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: You
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China Co-innovation Center of Neuroregeneration, Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, No. 2 Sipailou Road, Nanjing 210096, China liudongtom@gmail.com renjiec@seu.edu.cn.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Qixiu Road 19, Nantong 226001, China liudongtom@gmail.com renjiec@seu.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics* / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: C547183:MIRN10 microRNA, human; C577984:MIRN10 microRNA, zebrafish; D035683:MicroRNAs; D029961:Zebrafish Proteins; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish
keywords: Notch; angiogenesis; miR-10a; miR-10b; mib1