OncoTargets and Therapy (2020-11-01)

miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2

  • Pan X,
  • Li H,
  • Tan J,
  • Weng X,
  • Zhou L,
  • Weng Y,
  • Cao X

Journal volume & issue
Vol. Volume 13
pp. 11265 – 11275

Abstract

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Xiaohui Pan,1,* Haibo Li,1,* Jingxue Tan,1,* Xiaokun Weng,2 Li Zhou,1 Yiping Weng,1 Xiaojian Cao3 1Department of Orthopedics, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu 213003, People’s Republic of China; 2Department of Radiotherapy, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, Jiangsu 213003, People’s Republic of China; 3Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiping Weng; Xiaojian Cao Email [email protected]; [email protected]: MiR-1297 is reported to function as a tumor suppressor of various cancers. However, the role of miR-1297 in the development of osteosarcoma (OS) has not been elaborated. The purpose of this study was to investigate the functional effects of miR-1297 on OS progression and the underlying mechanism.Methods: The expression of protein and mRNA in OS cells was evaluated by Western blotting and quantitative real-time polymerase chain reaction. Cellular proliferation was investigated by cell counting kit-8, colony formation and apoptosis assays. Bioinformatics methods were used to predict target genes. The relationship between PFKFB2 and miR-1297 was demonstrated by dual-luciferase reporter assay. Metabolic changes in OS cells were monitored using an XF96 metabolic flux analyzer.Results: We found that miR-1297 was downregulated in OS and that lower expression of miR-1297 promoted proliferation and contributed to the Warburg effect in OS cells. Furthermore, we showed that silencing PFKFB2 inhibited proliferation and reduced aerobic glycolysis while overexpression of PFKFB2 reduced the anti-tumor function of miR-1297 in OS cells. Mechanistically, miR-1297 acted as a tumor suppressor in OS and reduced the expression of PFKFB2 by directly targeting its 3ʹUTR.Conclusion: The miR-1297/PFKFB2 axis regulated OS proliferation by controlling the Warburg effect. Our results revealed a previously undiscovered function of miR-1297 in OS, which strongly linked metabolic alterations with cancer progression. Targeting miR-1297 may become a promising therapeutic approach for OS.Keywords: osteosarcoma, miR-1297, PFKFB2, Warburg effect

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