Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective:To summarize our institutional experiences of screening and selecting potential recipients and living donors for uterine transplantation at a single center.Methods:A total of 102 patients were diagnosed as absolute uterine factor infertility (AUFI). Depending upon the outcomes of previous trials, 8 modules were selected for surveying. A registration form was distributed for subjects at outpatient clinics or through telephone consultations for clinical trials of uterus transplantation between November 2018 and October 2019. The relevant information was collected and entered into a dedicated system for data processing.Results:The number of eligible subjects was 84 and the number of recipients with potential donors 37. The average age of potential recipients was 26.0(18-47) years. Among potential recipients, 76(90.5%) had congenital AUFI and 8(9.5%) acquired AUFI. For potential donors with available organs, the average age was 47.5(32-64) years and the proportion of menopausal or peri-menopausal status 56.8%.Conclusions:Currently large demands and sufficient supports for conducting clinical trials of uterine transplantation are available in China. However, inherent deficiencies persist in organ donor population reserves and preoperative screening protocols, such as donor age and subjective/objective factors of participants. During clinical trials of uterine transplantation, preoperative screening should be performed for expanding the screening scope, extending the screening time and popularizing the screening knowledge to boost the success rate.