Down-Regulation of UBE2T Can Enhance Irradiation Sensitivity of Osteosarcoma in Vitro and Vivo

Abstract

Background: Radiotherapy is widely used in patients with osteosarcoma who are not eligible for surgery. However, the therapeutic efficacy of radiotherapy is unsatisfactory. UBE2T is a ubiquitin binding the enzyme E2T which, in turn binds the E3 ubiquitin ligase and induces degradation or functional changes in the substrate. Several recent studies have shown that UBE2T may play a key role as an oncogene in various tumors. Methods: The expression of UBE2T was explored by Gene Expression Omnibus (GEO) database analysis and real-time quantitative PCR (RT-qPCR). UBE2T upregulation in human osteosarcoma was confirmed by immunohistochemical analysis. Small interfering (si) RNA-mediated suppression of UBE2T affected the proliferation and cell cycle of osteosarcoma cells. Downregulation of UBE2T combined with radiation affects the clone formation, migration and apoptosis of osteosarcoma cells. MG-63 cells with the UBE2T knockout were injected into nude mice to induce a xenograft mode. Findings: UBE2T was highly expressed in human osteosarcoma. Suppression of UBE2T inhibited osteosarcoma cell proliferation and induced cell cycle arrest at the G2/M phase. Downregulation of UBE2T combined with radiation may substantially inhibit clonal formation and migration and promote apoptosis of osteosarcoma cells in vitro and vivo. Interpretation: The results indicated that downregulation of UBE2T may enhance osteosarcoma radiosensitivity and serve as a new target for osteosarcoma radiotherapy. Funding: This work was supported Youth Natural Science Foundation of China (No.81700144 ), the Natural Science Foundation of Shandong Province (ZR2014HM093). Declaration of Interest: The authors have declared that no conflict of interest. Ethical Approval: Informed consent was obtained from all patients participating in the present study which was conducted according to the guidelines and with the approval of the Medical Ethics Committee of Jinan Central Hospital.