UBE2C mediated radiotherapy resistance of head and neck squamous cell carcinoma by regulating oxidative-stress-relative apoptosis

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.

System analysis identifies UBE2C as a novel oncogene target for adrenocortical carcinoma

“…Accumulating evidence also suggested that the high expression of UBE2C is strongly related to poor prognosis in patients with breast cancer [ 24 , 27 ], lung adenocarcinoma [ 28 ] or gastric cancer [ 29 ]. On the one hand, based on the description of hallmarks of cancer proposed by Professor Douglas Hanahan [ 30 ], it has been confirmed that UBE2C can promote tumor growth [ 31 ], angiogenesis [ 32 ], tumor metastasis [ 33 , 34 ], anchorage-independent growth [ 35 ], stemness [ 36 ], resist apoptosis [ 37 , 38 ], induce immunosuppressive microenvironment [ 39 ], and enhance glycolytic activity [ 40 , 41 ]. On the other hand, high expression of UBE2C will lead to treatment failure attributed to overactive anchorage-independent growth and reduced oxidative stress-induced cell apoptosis resulting in chemotherapy resistance [ 35 ], and reduce radiosensitivity [ 38 ], respectively.…”

“…On the one hand, based on the description of hallmarks of cancer proposed by Professor Douglas Hanahan [ 30 ], it has been confirmed that UBE2C can promote tumor growth [ 31 ], angiogenesis [ 32 ], tumor metastasis [ 33 , 34 ], anchorage-independent growth [ 35 ], stemness [ 36 ], resist apoptosis [ 37 , 38 ], induce immunosuppressive microenvironment [ 39 ], and enhance glycolytic activity [ 40 , 41 ]. On the other hand, high expression of UBE2C will lead to treatment failure attributed to overactive anchorage-independent growth and reduced oxidative stress-induced cell apoptosis resulting in chemotherapy resistance [ 35 ], and reduce radiosensitivity [ 38 ], respectively. In short, a series of studies shown that UBE2C is highly expressed in tumors tissues and able to promote tumor progression.…”