Ubiquitin-conjugating enzyme E2C (UBE2C) plays important roles in tumor progression; nevertheless, its function in endometrial cancer remains unclear. This study elucidated the impact of UBE2C on endometrial cancer and its underlying mechanism. Human endometrial cancer and normal endometrial tissues were acquired from patients at Wuhan Union Hospital and UBE2C expression was detected by Western blotting and qRT-PCR. Endometrial cancer cells were transfected with a UBE2C overexpression plasmid or UBE2C-specific short hairpin RNA (shRNA) to up-or downregulate UBE2C expression, respectively. CCK8 and transwell assays were applied to assess the effects of UBE2C on cell proliferation, migration, and invasion. We found a significant elevation of UBE2C expression in patients with endometrial cancer, and that UBE2C upregulation was associated with advanced histologic grade, FIGO stage, recurrence, and shorter overall survival. UBE2C knockdown inhibited endometrial cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), whereas UBE2C overexpression exerted the opposite effects. UBE2C downregulation increased p53 and its downstream p21 expression, with p53 overexpression reversing the EMT-promoting effects of UBE2C. UBE2C enhanced p53 ubiquitination to facilitate its degradation in endometrial cancer cells. Estradiol (E2) induced UBE2C expression via estrogen receptor a, which binds directly to the UBE2C promoter element. Silencing of UBE2C inhibited E2-promoted migration, invasion, and EMT in vitro and in vivo.Implications: UBE2C-mediated tumor EMT promotion by estrogen is a novel mechanism for the progression of estrogen-induced endometrial cancer, which could offer new biomarkers for diagnosis and therapy of endometrial cancer in the future.

Human papillomavirus (HPV) has been the leading cause of cervical cancer for over 25 years. Approximately 5.5–11% of all cervical cancers are reported to be HPV-negative, which can be attributed to truly negative and false-negative results. The truly HPV-negative cervical cancers are almost all cervical adenocarcinomas with unclear etiology. False HPV negativity can arise from histological misclassification, latent HPV infection, disruption of the targeting fragment, non-high risk HPV infection, and HPV testing methods. HPV-negative cervical cancers are often diagnosed at an advanced FIGO stage and have a poor prognosis; thus, the management of these cases requires greater attention.

Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS.NF2 schwannoma model | anti-VEGF | neurological function | radiation