PUBLICATION
MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis
- Authors
- 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.
- ID
- ZDB-PUB-160131-2
- 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
-
- Oligonucleotide Array Sequence Analysis/methods
- Cell Proliferation/genetics*
- Cell Proliferation/physiology
- Neovascularization, Physiologic*
- MicroRNAs/genetics*
- PubMed
- 26825552 Full text @ Cardiovasc. Res.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping