miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib

Abstract

Leisheng Wang,1,* He En,2,* Lei Yang,3 Yanbing Zhang,2 Baisheng Sun,4 Jianjiang Gao51Department of Orthopedics, Yantaishan Hospital, Yantai, Shandong Province 264000, People’s Republic of China; 2Department of Outpatient, The 81st Group Army Hospital of Chinese People’s Liberation Army, Zhangjiakou City, Hebei Province, People’s Republic of China; 3Department of Outpatient, The 80th Group Army Hospital of Chinese People’s Liberation Army (formerly the 89th Hospital of the People’s Liberation Army), Weifang City, Shandong Province, People’s Republic of China; 4Department of Emergency, The Fifth Medical Center of the General Hospital of the Chinese People’s Liberation Army (formerly the 307th Hospital of the People’s Liberation Army), Beijing 100071, People’s Republic of China; 5Department of Emergency, Haiyang People’s Hospital, Haiyang, Shandong 265100, People’s Republic of ChinaCorrespondence: Jianjiang GaoDepartment of Emergency, Haiyang People’s Hospital, No. 73 Haiyang Road, Haiyang, Shandong Province 265100, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]*These authors contributed equally to this workBackground: Osteosarcoma (OSA), the most common primary bone malignancy, is characterized by a wide spectrum of complicated pathologies and frequent distal metastasis and causes death in adolescents and young adults worldwide. Antitumor drug treatment strategies include various cytotoxic chemotherapy drugs, while molecular targeted therapy for OSA is currently less used. The present work revealed the role played by the miR-596/Survivin axis in affecting the sensitivity of OSA cells to anlotinib, a novel molecular targeting agent.Methods: By virtual screening, we found that miR-596 might target Survivin by using an online tool (miRDB). RNA levels of miR-596 and Survivin in clinical specimens were examined with qPCR. The effect of miR-596 on anlotinib’s antitumor effect was examined with MTT experiments, the subcutaneous tumor model, or the intramuscular tumor model.Results: Overexpression of miR-596 via lentiviral particles repressed the protein level of Survivin in U2OS cells. Transfection of miR-596 enhanced the antitumor effect of anlotinib on U2OS cells or five cell lines derived from OSA patients.Conclusion: miR-596 targets Survivin and enhances the antitumor effect of anlotinib on OSA cells.Keywords: osteosarcoma cell, microRNAs, Survivin, molecular targeting agents, anlotinib

Keywords

• osteosarcoma cell
• microRNAs
• Survivin
• molecular targeting agents
• anlotinib