ZFIN ID: ZDB-PUB-160131-2
MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis
Wang, X., Ling, C.C., Li, L., Qin, Y., Qi, J., Liu, X., You, B., Shi, Y., Zhang, J., Jiang, Q., Xu, H., Sun, C., You, Y., Chai, R., Liu, D.
Date: 2016
Source: Cardiovascular research   110(1): 140-50 (Journal)
Registered Authors: Jiang, Qiu, Liu, Dong, Qi, Jialing, Qin, Yinyin, Shi, Yunwei, Wang, Xin, Xu, Hui
Keywords: Notch, angiogenesis, miR-10a, miR-10b, mib1
MeSH Terms:
  • Animals
  • Cell Proliferation/genetics*
  • Cell Proliferation/physiology
  • Endothelial Cells/metabolism*
  • Humans
  • MicroRNAs/genetics*
  • MicroRNAs/metabolism
  • Morphogenesis/physiology
  • Neovascularization, Physiologic*
  • Oligonucleotide Array Sequence Analysis/methods
  • Phenotype
  • Ubiquitin-Protein Ligases/genetics*
  • Ubiquitin-Protein Ligases/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics*
PubMed: 26825552 Full text @ Cardiovasc. Res.
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. In contrast, our data of real-time polymerase chain reaction, in situ hybridization and western blot analysis showed that neither mflt1 nor sflt1 levels were increased in miR-10 morphants at 24 nor 28 hours post fertilization. Thus, the regulatory mechanism of miR-10 in zebrafish angiogenesis needs to be further addressed. Firstly we demonstrated that miR-10a and miR-10b (miR-10a/10b) was highly enriched in embryonic zebrafish endothelial cells (ECs). Subsequently we proved loss of miR-10a/10b impaired blood vessel outgrowth through regulating tip cell behaviors. 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 regulate human ECs behavior through targeting Mib1 as well. Taken together, these results indicate that miR-10 regulates the angiogenic behavior in a Notch-dependent manner by directly targeting mib1.