CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis
Authors Gao Y, Ma H, Gao Y, Tao K, Fu L, Ren R, Hu X, Kou M, Chen B, Shi J, Wen Y
Received 2 January 2020
Accepted for publication 6 August 2020
Published 11 September 2020 Volume 2020:12 Pages 8287—8302
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
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 work
Correspondence: Junjun Shi Tel/fax +86 0351 6125623
Yunpeng Wen Tel/fax +86 0351 6185361
Background: 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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]