Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death.

BACKGROUND/AIMS: SUMOylation is a dynamic process and reversed by the activity of SUMO-specific proteases (SENPs) family. SENP1, a member of this family, is highly expressed and plays oncogenic roles in diverse cancers including prostate cancer. However, the SENP1-transgenic mice exhibit aberrant transformation of the mouse prostate gland but do not develop cancer. Cellular Stress Response 1 (CSR1) is a tumor suppressor gene and frequently deleted in prostate cancers. Overexpression of CSR1 in prostate cancer cells inhibits colony formation, anchorage-independent growth and induces cell death. METHODS: The relationship between CSR1 and SENP1 were determined by immunoprecipitation-based proteomics screen and verified by GST-pull down assay. In vivo SUMOylation assay was used to detect the direct effect of SENP1 in the regulation of CSR1. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Senp1-/- and CSR1-/- PC3 cells. FACS assay was used to determine the apoptosis ratio of cells after transfection. RESULTS: CSR1 is SUMOylated at K582 and rapid ubiquitinated and degradated in prostate cancer cells. SENP1 interacts with and deSUMOylates CSR1 to prevent its degradation and enhances CSR1-dependent prostate cancer cell death. CONCLUSION: Thus, our data indicates that CSR1 is a critical SUMOylated substrate of SENP1 that might partially explain the controversial roles of SENP1 in prostate cancer development.

[Meatoplasty with pedicle flap for meatal stenosis secondary to chronic balanitis].

OBJECTIVE: To evaluate the effect of meatoplasty with the pedicle flap in the treatment of meatal stenosis secondary to chronic balanitis. METHODS: We retrospectively analyzed 32 cases of meatal stenosis secondary to chronic balanitis treated by meato- plasty with the pedicle flap. All the patients had a history of chronic balanitis and had received meatal dilatation or simple ventral mea- totomy without significant effect. Their mean maximum urinary flow rate (Qmax) was (4.3 ± 2.4) ml/s. During the operation, A "/\"-shaped incision was made in the healthy epidermis and a flap was harvested from the frenulum. After complete removal of the scar, the flap was placed into the urethral wall, followed by reconstruction of the external urethral orifice. RESULTS: The patients were fol- lowed up for 6 to 30 months, which revealed smooth urination in all the patients with Qmax of (26.7 ± 4.5) ml/s and normal erectile function and uresiesthesis. CONCLUSION: With little invasiveness and few complications, meatoplasty with the pedicle flap is an ideal surgical method for the treatment of meatal stenosis secondary to chronic balanitis. However, there might be some change in the normal appearance of the balanus postoperatively, and its long-term effect needs further observation.