Circ_0056285 Regulates Proliferation, Apoptosis and Glycolysis of Osteosarcoma Cells via miR-1244/TRIM44 Axis
Authors Huo S, Dou D
Received 5 November 2020
Accepted for publication 13 January 2021
Published 10 February 2021 Volume 2021:13 Pages 1257—1270
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Eileen O'Reilly
Shousong Huo,1 Dongmei Dou2
1Department of Orthopaedic, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, People’s Republic of China; 2Institute of Chronic Disease Risk Assessment, Henan University, Jinming Campus, Kaifeng, 475000, Henan, People’s Republic of China
Correspondence: Dongmei Dou
Institute of Chronic Disease Risk Assessment, Henan University, Jinming Campus, Kaifeng, 475000, Henan, People’s Republic of China
Background: Osteosarcoma (OS) is a common malignant bone cancer that occurs in adolescents and children. Circular RNAs (circRNAs) are important regulators of tumorigenesis and development. This study aimed to explore the role and molecular basis of circ_0056285 in OS.
Methods: The levels of circ_0056285, miR-1244 and tripartite motif containing 44 (TRIM44) were determined by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis was assessed by flow cytometry and caspase 3and caspase 9 activity assay kits. Glucose uptake, lactate product and ATP level were examined using commercial kits. Hexokinase II (HK2) and lactate dehydrogenase A (LDHA) levels were measured by Western blot assay. The interaction among circ_0056285, miR-1244 and TRIM44 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. Xenograft experiment was conducted to explore tumor growth in vivo. Exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western blot. The diagnostic value of exosomal circ_0056285 was evaluated by receiver operating characteristic (ROC) curve.
Results: Circ_0056285 and TRIM44 were up-regulated, and miR-1244 was down-regulated in OS tissues and cells. Circ_0056285 silencing inhibited proliferation and glycolysis and promoted apoptosis in OS cells. Also, circ_0056285 knockdown hindered proliferation and accelerated apoptosis in OS cells by regulating miR-1244/TRIM44 axis. Circ_0056285 depletion impeded tumor growth in vivo. Furthermore, ROC curve showed that circ_0056285 might be a diagnostic biomarker in OS.
Conclusion: Circ_0056285 facilitated OS progression by sponging miR-1244 and increasing TRIM44 expression, providing a promising therapeutic target for OS.
Keywords: osteosarcoma, circ_0056285, miR-1244, TRIM44, progression
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