Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells

• Main Authors: Yuan Q, Yu H, Chen J, Song X, Sun L
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: OncoTargets and Therapy
• Subjects: pyruvate kinase m2; mir-1294; osteosarcoma; cell proliferation; cell apoptosis; tumorigenesis
• Online Access: https://www.dovepress.com/antitumor-effect-of-mir-1294pyruvate-kinase-m2-signaling-cascade-in-os-peer-reviewed-article-OTT

Quan Yuan,1 Honghao Yu,1 Jianhua Chen,1 Xiaoyu Song,2 Li Sun3 1Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Institute of Translational Medicine, China Medical University, Shenyang 110122, People’s Republic of China; 3Department of Nephrology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Quan YuanDepartment of Orthopedic Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110001, People’s Republic of ChinaEmail [e-mail]: MicroRNAs (miRNAs) can act as negative regulators of gene expression, and play a crucial role in cancer progression. The aim of this study was to investigate the role of miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma cells in vitro and in vivo.Methods: The function of miR-1294 and its association with PKM2 in osteosarcoma cells were studied by real-time PCR, CCK-8, Western blot, scratch test, transwell assay, flow cytometry, and dual-luciferase reporter assays. The effect of miR-1294 on tumor growth in vivo was evaluated in a subcutaneous xenograft model of osteosarcoma.Results: miR-1294 was downregulated in osteosarcoma cells. Forced overexpression of miR-1294 inhibited cell proliferation, migration, and invasion, and induced G0/G1 arrest and apoptosis. Consistently, protein expression levels of proliferating cell nuclear antigen, c-Myc, cyclin D1, active matrix metalloproteinase 2, and active matrix metalloproteinase 9 were decreased, and cleaved caspase 3 and cleaved PARP were increased following miR-1294 overexpression. Moreover, we demonstrated that PKM2 was a target of miR-1294 in osteosarcoma cells, and the effects caused by miR-1294 mimic were reversed by the overexpression of PKM2. Furthermore, we found that upregulation of miR-1294 inhibited tumorigenesis of osteosarcoma cells in vivo, which was accompanied by downregulation of PKM2.Conclusion: Our results revealed that miR-1294/PKM2 signaling cascade exerts important roles in the regulation of tumor progression, implying that this pathway may serve as a potential therapeutic target in osteosarcoma.Keywords: pyruvate kinase M2, miR-1294, osteosarcoma, cell proliferation, cell apoptosis, tumorigenesis