UBE2C通过调控氧化应激和DNA损伤介导头颈部鳞癌放疗抵抗的机制研究

Abstract

Purpose Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene. Method TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression. Result The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation. Conclusions Through the RT-PCR, WB, cell viability experiment, migration, invasion, and in vivo experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.