Yun Li

TCEB3 initiates ovarian cancer apoptosis by mediating ubiquitination and degradation of MCL‐1

Abstract Platinum resistance remains a major contributor to the poor prognosis of ovarian cancer. Anti‐apoptotic protein myeloid cell leukemia‐1 (MCL‐1) has emerged as a promising target for overcoming drug resistance, but different cancer cells utilize distinct protein degradation pathways to alter MCL‐1 level. We systematically investigated E3 ligases to identify novel candidates that mediate platinum resistance in ovarian cancer. Transcription Elongation Factor B (TCEB3) has been identified as a novel E3 ligase recognition subunit that targets MCL‐1 in the cytoplasm during platinum treatment other than its traditional function of targeting the Pol II in the nuclear compartment. TCEB3 expression is downregulated in platinum‐resistant cell lines and this low expression is associated with poor prognosis. The ubiquitination of MCL‐1 induced by TCEB3 leads to cell death in ovarian cancer. Moreover, platinum treatment increased the cytoplasm proportion of TCEB3, and the cytoplasm localization of TCEB3 is important for its targeting of MCL‐1. This study emphasizes the dual function of TCEB3 in homeostasis maintenance and in cell fate determination under different conditions, and provides a new insight into drug resistance in ovarian cancer.

Effect of PARP Inhibitor Combined with Bevacizumab on Platinum-Resistant Recurrent Ovarian Epithelial Carcinoma

Objective. This study was aimed at investigating the efficacy of PARP inhibitor combined with bevacizumab in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma. Methods. A total of 84 patients with platinum-resistant recurrent ovarian epithelial carcinoma treated in our hospital from May 2017 to June 2018 were selected as the research objects. The patients were divided into observation group ( n = 42 ) and control group ( n = 42 ) according to random number table method. The observation group was treated with olaparib combined with bevacizumab, while the control group was treated with albumin-bound paclitaxel combined with bevacizumab, and the clinical efficacy of the two groups was observed. The levels of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and epididymal protein 4 (HE4) were determined. The levels of miRNA124, mirNA-21, and miRNA-203 in the two groups were detected. The incidence of adverse reactions was compared between the two groups. The quality of life of the two groups was assessed using FACT-G scale. The drug safety of the two groups was observed. All patients were followed up for 3 years, and the survival time of the two groups was recorded. The Kaplan-Meier method was used to analyze the survival of the two groups. Results. The overall response rate (ORR) (69.05%) and disease control rate (DCR) (88.10%) of the observation group were higher than those of the control group (40.48% and 66.67%), and the differences were statistically significant (both P < 0.05 ). After treatment, the levels of serum CA125, CA199, HE4, miRNA124, miRNA-21, and miRNA-203 and the improvement degree of quality of life score in the observation group were greater than those in the control group, with statistical significances (all P < 0.05 ).The 1-year, 2-year, and 3-year survival rates of the observation group (97.62%, 88.10%, and 80.95%) were higher than those of the control group (71.43%, 57.14%, and 47.62%), with statistical significances (all P > 0.05 ). Conclusion. PARP inhibitor combined with bevacizumab had good effect in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma and can effectively improve the survival time and quality of life of patients.