Background Prostate cancer (PCa) is an age‐related malignancy with a high incidence and mortality rate due to lack of efficacy drugs for its therapy in late castration‐resistant stage. Sirtuin 2 (SIRT2), a NAD+‐dependent protein deacetylase, is associated with age‐related diseases. However, SIRT2 roles in PCa are unclear yet. Methods Data of SIRT2 expression were extracted from TCGA cohort and GSE54460 cohort. Realtime quantitative PCR and immunohistochemistry were employed to analyze the expression of SIRT2 in PCa tissues. Cell counting Kit‐8 assay, lentiviral transduction, flow cytometry, transwell experiments, western blot and metabolomic analysis were performed to explore the functions of SIRT2. Results SIRT2 exhibited increased expression in castration‐resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Overexpression of SIRT2 promoted cell proliferation, the proportion of S phase, migration and invasion, and reduced apoptosis rate. The increased phosphorylated ERK1/2 indicated the regulation of SIRT2 to cell proliferation, migration and invasion through activation of ERK1/2 pathway. Furthermore, SIRT2 affected cell metabolic profile and induces lactosylceramide production through upregulation of B4GALT5, which further contributes cell migration and invasion. Conclusions Our data suggested that SIRT2 is overexpressed in CRPC and NEPC and could promote cell growth and migration through activating ERK1/2 pathway and inducing lactosylceramide production, indicating that SIRT2 has the potential to be a new target for the treatment of PCa.
Purpose: To compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi larger than 10 mm. Methods: This is a retrospective study that incorporates medical record review with an outcomes management database.163 patients who underwent MPCNL and 137 patients who underwent FURS were identified from January 2017 to December 2021. Demographic data,operation time,hospitalization time,stone free rate and complication rate were collected and analyzed. Results: Preoperative general data of sex, age, BMI,serum creatinine, time of stone existence,stone hardness,stone diameter preoperative hydronephrosis and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group.All of the MPCNL or FURS surgeries in two groups were successfully completed, with no one returned to opening or other surgery.Patients treated by MPCNL had significantly shorter operation time (49.6 vs 72.4 minutes;P<0.001) but longer hospitalization time (9.1 vs 3.9days;P<0.001) than those treated by FURS.Stone free rate in the MPCNL group was better than that of the FURS group(90.8% vs 71.5%;P<0.001). There was no statistically significant difference in complication rate between two groups(13.5% vs 15.3%;P=0.741). Conclusion: Both MPCNL and FURS are effective and safe surgical options for patients with single upper ureteral calculi larger than 10 mm. FURS had shorter hospitalization time than MPCNL,but with a relatively lower stone free rate and longer operation time.There was no significant differences between two groups in complication rate. Trial registration: No.
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