PUBLICATION
miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo
- Authors
- Pedrioli, D.M.L., Karpanen, T., Dabouras, V., Jurisic, G., van de Hoek, G., Shin, J.W., Marino, D., Kälin, R.E., Leidel, S., Cinelli, P., Schulte-Merker, S., Brändli, A.W., and Detmar, M.
- ID
- ZDB-PUB-100525-2
- Date
- 2010
- Source
- Molecular and cellular biology 30(14): 3620-3634 (Journal)
- Registered Authors
- Karpanen, Terhi, Schulte-Merker, Stefan
- Keywords
- miRNA post-transcriptional regulation, vascular development, lymphangiogenesis, PROX1, miR-31
- MeSH Terms
-
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- In Vitro Techniques
- Cells, Cultured
- Female
- Polymerase Chain Reaction
- Blood Vessels/cytology
- Blood Vessels/growth & development
- Blood Vessels/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Lymphatic System/cytology*
- Lymphatic System/growth & development*
- Lymphatic System/metabolism
- MicroRNAs/genetics*
- MicroRNAs/metabolism
- Base Sequence
- In Situ Hybridization
- Cell Differentiation/genetics
- Cell Differentiation/physiology
- RNA Processing, Post-Transcriptional
- Humans
- Gene Expression Profiling
- Animals, Genetically Modified
- Xenopus laevis/embryology
- Xenopus laevis/genetics
- Xenopus laevis/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Endothelial Cells/cytology*
- Endothelial Cells/metabolism*
- Mice
- Animals
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism
- PubMed
- 20479124 Full text @ Mol. Cell. Biol.
Citation
Pedrioli, D.M.L., Karpanen, T., Dabouras, V., Jurisic, G., van de Hoek, G., Shin, J.W., Marino, D., Kälin, R.E., Leidel, S., Cinelli, P., Schulte-Merker, S., Brändli, A.W., and Detmar, M. (2010) miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Molecular and cellular biology. 30(14):3620-3634.
Abstract
The lymphatic vascular system maintains tissue fluid homeostasis, helps mediate afferent immune responses and promotes cancer metastasis. To address the role microRNAs (miRNAs) play in the development and function of lymphatic vascular system, we defined the in vitro miRNA expression profiles of primary human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) and identified 4 BVEC-signature and 2 LEC-signature miRNAs. Their vascular lineage-specific expression patterns were confirmed in vivo by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Functional characterization of the BVEC-signature miRNA, miR-31, identified a novel BVEC-specific post-transcriptional regulatory mechanism that inhibits the expression of lymphatic-specific transcripts in vitro. We demonstrate that suppression of lymphatic differentiation is partially mediated via direct repression of PROX1, a transcription factor that functions as a master regulator of lymphatic lineage-specific differentiation. Finally, in vivo studies in Xenopus and zebrafish demonstrated that gain-of-miR-31 function impaired venous sprouting and lymphatic vascular development. Thus, highlighting the importance of miR-31 as a negative regulator of lymphatic development. Collectively, our findings identify miR-31 is a potent regulator of vascular lineage-specific differentiation and development in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping