Circular RNA circ-NT5C2 acts as an oncogene in osteosarcoma proliferation and metastasis through targeting miR-448

Abstract

// Xunfa Liu 1 , Yuanbo Zhong 1 , Jifeng Li 2 and Aijun Shan 1 1 Department of Emergency, Second Clinical Medical College, Shenzhen People’s Hospital, Jinan University, Shenzhen, 518020, China 2 College of Basic Medicine, Jinan University, Guangzhou, Guangdong, 510632, China Correspondence to: Aijun Shan, email: shanaijun_emerg@yeah.net Keywords: osteosarcoma; circular RNA; circ-NT5C2; circRNA microarray; miR-448 Received: July 28, 2017     Accepted: September 20, 2017     Published: October 30, 2017 ABSTRACT Circular RNAs (circRNAs) are a type of endogenous noncoding RNA which have been verified to participate in numerous pathophysiological processes. However, the underlying role of circRNAs in osteosarcoma tissue is still unidentified. Our study aims to investigate the circRNA expression profiles in osteosarcoma tissue and investigate the physiological functions of circRNAs. Human circRNAs microarray analysis showed that 785 differently expressed circRNAs were distinguished in osteosarcoma tissue and adjacent non-tumor tissue with 2 fold change. Circ-NT5C2 was validated to be up-regulated expressed in 52 pairs of osteosarcoma tissue and cell lines. Furthermore, the enforced expression of circ-NT5C2 could act as a valuable diagnostic marker for osteosarcoma detection with AUC (area under the ROC curve) value of 0.753. Functional validation experiments verified that circ-NT5C2 silencing suppressed the proliferation and invasion, and promoted apoptosis of osteosarcoma cells in vitro . In vivo , circ-NT5C2 silencing inhibited the tumor growth. Bioinformatics analysis and rescue experiments indicated that circ-NT5C2 sponged miR-448, which was confirmed by luciferase reporter assay and RT-PCR assay. Overall, our study investigates the circRNAs expression profiles and determines the function of circ-NT5C2 in osteosarcoma tumorigenesis, which might serve as a novel therapeutic target of osteosarcoma patients.