miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells
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Zaidoun Salah1,2,*, Rand Arafeh1,*, Vadim Maximov1, Marco Galasso3, Saleh Khawaled1, Samah Abou-Sharieha1, Stefano Volinia3,4, Kevin B. Jones5, Carlo M. Croce4, Rami I. Aqeilan1,4
1The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel
2Al Quds-Bard College, Al-Quds University, Abu Dies, East Jerusalem, Palestine
3Biosystems Analysis, LTTA, Department of Morphology, Surgery and Experimental Medicine, Università degli Studi, Ferrara, Italy
4Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, USA
5Huntsman Cancer Institute at the University of Utah, Salt Lake City, USA
*These authors have contributed equally to this work
Rami I. Aqeilan, e-mail: [email protected]
Keywords: osteosarcoma, metastasis, miR-27a, CBFA2T3, star miRNA
Received: December 05, 2014 Accepted: January 01, 2015 Published: February 28, 2015
Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR-27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR-27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.
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