BackgroundBreast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Several zinc finger proteins were shown to mediate the ubiquitination process and modulate protein stability. Thus, we further explore the function of Zinc finger protein 213 on ER alpha protein stability and tamoxifen resistance.MethodsCCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, real-time quantitative PCR, and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipitation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha.ResultsWe identified ZNF213 as a novel zinc finger protein, which modulated ER alpha protein. ZNF213 expression correlated with poor outcome in endocrine treated patients. ZNF213 depletion inhibited ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies showed ZNF213 located in cytosol and nuclear, which modulated ER alpha stability via inhibiting ER alpha K48-linked ubiquitination.ConclusionsOur study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.

Purpose: To investigate the influence of chloroprocaine combined with morphine on the analgesic effects, adverse reactions and inflammation factors in patients receiving transurethral resection of the prostate (TURP).Methods: A total of 80 patients with benign prostatic hyperplasia (BPH) in the Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China, were divided into morphine group and combination-therapy group (morphine combined with chloroprocaine). Pain index, changes in inflammatory factors and incidence of adverse reactions in the two groups of patients were assessed.Results: The morphine group and combination-therapy group showed basic profile prior to the treatments. Visual Analogue Scale (VAS) scores before operation and 6 h after operation in the morphine group were similar to those in the combination-therapy group, but the scores at 12, 24 and 48 h after operation in the combination-therapy group were significantly lower than those in the morphine group. Similarly, the combination-therapy group showed lower levels of substance P (SP) and bradykinin (BK) at 12, 24 and 48 h after operation than the morphine group (p < 0.05). Both groups exhibited similar levels of serum inflammatory factors before the operation, but the levels decreased in the combination-therapy group when compared with those in the morphine group after operation (p < 0.05). The combination-therapy group also showed a lower incidence of adverse reactions than the morphine group.Conclusion: Chloroprocaine combined with morphine effectively ameliorates postoperative pain, lowers secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10), and decreases the incidence of postoperative adverse reactions, thus affording a high level of safety after operation.

Background Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Methods CCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, QPCR and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipitation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha. Results we identified ZNF213 as a novel zinc finger protein, which modulated ER alpha protein. ZNF213 expression correlated with poor outcome in endocrine treated patients. ZNF213 depletion inhibited ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies showed ZNF213 located in cytosol and nuclear, which modulated ER alpha stability via inhibiting ER alpha K48-linked ubiquitination. Conclusions Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.