Identification and functional characterization of circRNA-0008717 as an oncogene in osteosarcoma through sponging miR-203

// Xiang Zhou 1 , Dimple Natino 2 , Zili Qin 3 , Dong Wang 1 , Zhen Tian 4 , Xuan Cai 1 , Bo Wang 5 and Xijing He 1 1 Department of Orthopaedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China 2 Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA 3 Department of Otolaryngology, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 4 Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China 5 Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi'an, China Correspondence to: Xijing He, email: xijing_h@vip.tom.com Keywords: osteosarcoma; circRNA-0008717; miR-203; Bmi-1 Received: September 11, 2017 Accepted: November 16, 2017 Epub: December 20, 2017 Published: April 27, 2018 ABSTRACT Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in osteosarcoma tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on osteosarcoma carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in osteosarcoma tissue and circRNA-0008717 was identified as one circRNA significantly upregulated in osteosarcoma tissue. Osteosarcoma patients with high circRNA-0008717 expression had shortened survival. Gain and loss functional assays suggested that knockdown of circRNA-0008717 suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. By using biotin-labeled circRNA-0008717 probe to perform RNA precipitation in osteosarcoma cells, we identified miR-203 as the circ0008717-associated microRNA. Subsequently, Bmi-1 was identified as the functional target of miR-203. In addition, overexpression of circRNA-0008717 in osteosarcoma could elevate Bmi-1 expression, resulting in the promotion of osteosarcoma cell proliferation and invasion. Furthermore, the tumor promoting effect of circRNA-0008717 was abolished by miR-203 mimics or Bmi-1 silencing vector. In conclusion, circRNA-0008717 plays an oncogenic role in osteosarcoma and may serve as a promising prognostic biomarker for osteosarcoma patients. Therefore, silence of circRNA-0008717 could be a future direction to develop a novel treatment strategy.