Gao, Yuanpeng, Ma, Haixia, Gao, Yan, Tao, Kai, Fu, Liyan, Ren, Ruimin, Hu, Xingui, Kou, Min, Chen, Bin, Shi, Junjun, and Wen, Yunpeng
Yuanpeng Gao,1,* Haixia Ma,2,* Yan Gao,3 Kai Tao,4 Liyan Fu,5 Ruimin Ren,6 Xingui Hu,7 Min Kou,8 Bin Chen,1 Junjun Shi,1 Yunpeng Wen9 1Department of Orthopaedics,The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Tumor Hospital of Shanxi, Taiyuan, People’s Republic of China; 3Department of VitreoretinalSurgery, Shanxi Eye Hospital, Taiyuan, People’s Republic of China; 4Department of Digestive Minimally Invasive Surgery, Tumor Hospital of Shanxi, Taiyuan, People’s Republic of China; 5Comprehensive Examination Department, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China; 6Department of Urology Surgery, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 7Department of Cardiology, Taiyuan Iron and Steel Group General Hospital, Taiyuan, People’s Republic of China; 8Department of Nephrology, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China; 9Department of Rehabilitation, Shanxi Huajin Orthopedic Hospital, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun Shi Tel/fax +86 0351 6125623Email gypfly147852@163.comYunpeng Wen Tel/fax +86 0351 6185361Email nmepvb@163.comBackground: Osteosarcoma (OS) is the most common bone tumor. Many studies have reported that circular RNAs (circRNAs) play an important role in the development of a variety of human cancers. However, the underlying mechanism of circ_0001721 in regulating osteosarcoma progression remains unknown.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001721, miR-372-3p, and mitogen-activated protein kinase 7 (MAPK7) in osteosarcoma tissues and cells. Besides, glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, separately. Cell migration and invasion were determined by transwell assay. Moreover, the protein levels of HK2 and epithelial-to-mesenchymal transition (EMT) markers were determined by Western blot analysis. The relationship between miR-372-3p and circ_0001721 or MAPK7 was predicated by starbase v3.0 and confirmed by dual-luciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assay. Murine xenograft model was established to investigate the role of circ_0001721 in vivo.Results: The levels of circ_0001721 and MAPK7 were upregulated in osteosarcoma tissues and cells, while miR-372-3p was downregulated. Knockdown of circ_0001721 inhibited glycolysis, cell proliferation, cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and promoted apoptosis. Circ_0001721 was validated as a sponge of miR-372-3p and mediated glycolysis, cell proliferation, apoptosis, migration, invasion, and EMT of osteosarcoma cells through miR-372-3p. MAPK7 was a target of miR-372-3p and overexpression of MAPK7 attenuated anti-cancer role of miR-372-3p in OS cells. Further studies revealed that circ_0001721 regulates MAPK7 expression via sponging miR-372-3-p. Finally, knockdown of circ_0001721 inhibited tumor progression in vivo.Conclusion: Circ_0001721 promoted osteosarcoma development through the miR-372-3p/MAPK7 axis.Keywords: circ_0001721, miR-372-3p, MAPK7, osteosarcoma