Abstract 16458: Micro RNA 221 and 222: An miRNA Cassette With Opposing Effects on Angiogenesis
Background: Micro RNAs (miRs) are small non-coding RNAs that regulate gene expression by degradation of mRNAs or inhibition of protein translation. Many miRs are co-expressed and co-regulated and some miRs have been shown to positively and negatively affect angiogenesis. Here we report that miR-221 and 222 are co-expressed but have completely opposite effects on angiogenesis.
Methods and Results: The expression of miR221 and miR222 were detected in human plasma and in cell culture using real-time qPCR with available primer-probe sets. Both miRs showed higher expression (miR221: 4 fold, p=0.03; miR222: 1.4 fold, p=0.05) in a subset of patients with the most severe form of peripheral arterial disease (PAD) when compared to other PAD patients. The forced overexpression in human endothelial cells with miR-221 mimic results in an increase in cell proliferation, increase cell viability and forms more tube like structures on matrigel assay under hypoxic serum starvation (HSS) compared to the negative control (p<0.01, p<0.01 and p<0.01 respectively). In contrast, knock-down by antagomiR-221 decreases cell proliferation and forms less tubes compared to the negative control (p<0.01 and p<0.01 respectively). Moreover, endothelial cells transfected with miR-222 significantly reduces cell proliferation, decreases cell viability and attenuates tube formation under HSS conditions (p=0.02, p=<0.01 and p<0.01 respectively). Knock down with antagomiR-222 increases cell proliferation and improves tube formation (p<0.01 and p=0.04 respectively) (figure).
Conclusion: Our data indicates that though co-expressed, miR-221 and 222 have opposing effects with miR-221 being proangiogenic and miR-222 being antiangiogenic. Thus miR-221 may serve as a potential target for ischemic diseases.
Author Disclosures: A. Cunningham: None. T. Wang: None. R. Lye: None. B. Annex: None.
- © 2014 by American Heart Association, Inc.