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Int. J. Mol. Sci. 2012, 13(2), 2063-2077; doi:10.3390/ijms13022063

ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a

1,*  and 2,*
1 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China 2 Research Laboratory of Virology, Immunology & Bioinformatics, Northwest A & F University, Xianyang 712100, Shaanxi, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 4 November 2011 / Revised: 3 February 2012 / Accepted: 7 February 2012 / Published: 15 February 2012
(This article belongs to the Special Issue Non-Coding RNAs)
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Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation and activate BMP signal pathway. The constitutively active ACVR1 is also found to be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial cells, which may cause the formation of FOP lesions. MicroRNAs (miRNAs) play an essential role in regulating cell differentiation. Here, we verified that miR-148a directly targeted the 3' UTR of ACVR1 mRNA by reporter gene assays and mutational analysis at the miRNA binding sites, and inhibited ACVR1 both at the protein level and mRNA level. Further, we verified that miR-148a could inhibit the mRNA expression of the Inhibitor of DNA binding (Id) gene family thereby suppressing the BMP signaling pathway. This study suggests miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against FOP.
Keywords: ACVR1; miR-148a; FOP; BMP; EndMT ACVR1; miR-148a; FOP; BMP; EndMT
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Song, H.; Wang, Q.; Wen, J.; Liu, S.; Gao, X.; Cheng, J.; Zhang, D. ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a. Int. J. Mol. Sci. 2012, 13, 2063-2077.

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