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Journal Article

Vascular importance of themiR-212/132 cluster.

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Ucar,  A.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Chowdhury,  K.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

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Citation

Kumarswamy, R., Volkmann, I., Beermann, J., Napp, L. C., Jabs, O., Bhayadia, R., et al. (2014). Vascular importance of themiR-212/132 cluster. European Heart Journal, 35(45), 3224-3231. doi:10.1093/eurheartj/ehu344.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-B4DD-D
Abstract
Rationale Many processes in endothelial cells including angiogenic responses are regulated by microRNAs. However, there is limited information available about their complex cross-talk in regulating certain endothelial functions. Aim The objective of this study is to identify endothelial functions of the pro-hypertrophic miR-212/132 cluster and its crosstalk with other microRNAs during development and disease. Methods and results We here show that anti-angiogenic stimulation by transforming growth factor-beta activates the microRNA-212/132 cluster by derepression of their transcriptional co-activator cAMP response element-binding protein (CREB)-binding protein (CBP) which is a novel target of a previously identified pro-angiogenic miRNA miR-30a-3p in endothelial cells. Surprisingly, despite having the same seed-sequence, miR-212 and miR-132 exerted differential effects on endothelial transcriptome regulation and cellular functions with stronger endothelial inhibitory effects caused by miR-212. These differences could be attributed to additional auxiliary binding of miR-212 to its targets. In vivo, deletion of the miR-212/132 cluster increased endothelial vasodilatory function, improved angiogenic responses during postnatal development and in adult mice. Conclusion Our results identify (i) a novel miRNA-cross-talk involving miR-30a-3p and miR-212, which led to suppression of important endothelial genes such as GAB1 and SIRT1 finally culminating in impaired endothelial function; and (ii) microRNAs may have different biological roles despite having the same seed sequence.