miR-181c associates with tumor relapse of high grade osteosarcoma

Abstract

// Federica Mori 1 , Andrea Sacconi 2 , Valeria Canu 2 , Federica Ganci 2 , Mariangela Novello 3 , Vincenzo Anelli 4 , Renato Covello 5 , Virginia Ferraresi 6 , Paola Muti 7 , Roberto Biagini 8 , Giovanni Blandino 2,7 and Sabrina Strano 1,7 1 Molecular Chemoprevention Unit, Regina Elena National Cancer Institute, Rome, Italy 2 Translational Oncogenomics, Regina Elena National Cancer Institute, Rome, Italy 3 Department of Pathology, Catholic University, Rome, Italy 4 UOC Radiology, Regina Elena National Cancer Institute, Rome, Italy 5 UOC Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy 6 Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy 7 Department of Oncology, McMaster University, Hamilton, ON, Canada 8 UOC Orthopedic Surgery, Regina Elena National Cancer Institute, Rome, Italy Correspondence: Giovanni Blandino, email: // Keywords : giant cell tumor, osteosarcoma, miRNA profiling, relapse Received : December 11, 2014 Accepted : February 17, 2015 Published : March 12, 2015 Abstract High-grade osteosarcoma (OS) is characterized by low incidence, high aggressiveness and moderate 5-years survival rate after aggressive poly-chemotherapy and surgery. Here we used miRNA profiling as a tool to possibly predict and monitor OS’s development and therapeutic outcome. First, we evaluated the altered expression of selected miRNAs from a case of Giant Cell Tumor (GCT) apparently evolved into an OS. We found that most of modulated miRs were associated with pathways of bone resorption and osteogenesis. miRNA expression also revealed that GCT and OS were distinct tumors. Second, we validated the observed miRNA profile in two independent casuistries of ten GCT (not evolved into malignant tumors) and sixteen OS patients. Interestingly, we found that miR-181c and other three miRNAs identified in the first step of the study were also consistently de-regulated in all OS patients. Ectopic expression of miR-181c reduced cell viability and enhanced chemotherapeutic-induced cell death of U2OS and SAOS2 cells. These findings indicate that: i) miRNAs aberrantly modulated in GCT could be predictive of its development into OS and ii) miRNAs expression could be useful to monitor the OS therapeutic outcome.