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 investigate the effect and mechanism of brain-derived neurotrophic factor (BDNF) pretreatment for reducing myocardial ischemia/reperfusion (I/R) injury in experiment rats.
Methods: Rat’s myocardial I/R model was established by left anterior descending artery ligation for 30min followed-by reperfusion for 180 min. The rats were divided into 5 groups:Sham operation group, I/R group and IR with BDNF pretreatment (1, 10, 100) nmol/(kg·ml) groups respectively. The LVSP, LVEDP, ±dp/dtmax were recorded after I/R;serum levels of LDH, CK and the cardiac tissue levels of MDA, SOD were examined;the ratios of left ventricular myocardial infarction area in different groups were observed by by Evans blue staining;cell apoptosis rates were evaluated by Tunel staining;the total-TrkB and p-TrkB in myocardium were detected by Western-blot analysis.
Result: Compared with I/R group, in 3 IR with BDNF pretreatment groups, LVSP, ±dp/dtmax were gradually increasing and LVEDP were gradually decreasing, all P<0.05;the leaking levels of LDH, CK and the content of MDA were gradually decreasing and the SOD activity was gradually increasing, all P<0.05;the average ratios of MI area/ischemic area were decreased from (47.54 ± 6.35)%to (28.68 ± 4.56)%, the apoptosis rates decreased from (37.89 ± 5.46)%to (10.24 ± 3.05)%, the level of p-trkB/Total-TrkB increased from (0.16 ± 0.03) to (0.42 ± 0.03), P<0.05.
Conclusion: BDNF pretreatment could maintain the cardiac function in experiment rats after I/R injury, it may reduce MI area, decrease oxidative damage and apoptosis, therefore, protect myocardial cells for reducing IR injury.