Small ubiquitin-like modifier protein-specific protease 1 and prostate cancer

Small ubiquitin-like modifier protein （SUMO） modification is a highly dynamic process, catalyzed by SUMO- specific activating （El）, conjugating （E2） and ligating （E3） enzymes, and reversed by a family of SUMO-specific proteases （SENPs）. There are six members of the human SENP family, and each SENP has different cellular locations and substrate specificities. However, the precise roles of SENPs in cellular processes have not been elucidated to date. This brief review will focus on recent advances pertaining to the identified targets of SENP 1 and its potential role in prostate cancer.

类泛素化蛋白酶1基因的表达与肝癌细胞株侵袭转移的关系

目的:研究类泛素化蛋白酶-1(sentrin-specific protease-1,SENP-1)基因在不同侵袭潜能肝细胞肝癌细胞株及人永生化肝细胞中mRNA和蛋白的表达水平及其与肝癌细胞侵袭能力的关系。方法:使用RT-PCR、Real-time PCR、Western blotting和免疫荧光方法对肝癌细胞株MHCC97L(低侵袭性)、MHCC97H和HCCLM3(高侵袭性)、SMMC-7721和HepG2(无明显侵袭性)SENP-1 mRNA和蛋白表达水平进行检测,以人永生化肝细胞株HL-7702为对照,分析SENP-1的表达与肝癌细胞株侵袭转移能力的关系。结果:RT-PCR和Real-time PCR检测结果显示,SENP-1 mRNA(F=5.658;P=0.042)和蛋白(F=88.909,P=0.000)在肝癌细胞株中的表达随着肝癌细胞株侵袭潜能的增高而增高;Western blotting检测结果显示,5种肝癌细胞株SENP-1蛋白水平均显著高于人永生化肝细胞株;免疫荧光法观察发现,SENP-1蛋白在肝癌细胞株内主要为胞质表达,部分胞核表达。结论:SENP-1基因在肝癌细胞株中的高表达可能具有促进肝癌细胞侵袭转移的作用。

SUMO特异性蛋白酶家族与肿瘤生物学行为的关系

SUMO化修饰是一个动态可逆的过程,需要特异性连接酶参与,其逆反应(去SUMO化)则是由一组SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)参与的催化解离。SUMO化修饰的靶蛋白分子与机体的发育、疾病,特别是肿瘤、代谢、炎症与免疫等密切相关,且SENPs在SUMO蛋白的加工成熟和靶蛋白去SUMO化修饰中发挥重要作用。该文就SENPs家族蛋白在肿瘤发生发展中的作用和机制进行综述。

Over-expression of small ubiquitin-like modifier proteases 1 predicts chemo-sensitivity and poor survival in non-small cell lung cancer

Background Non-small cell lung cancer （NSCLC） is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression of small ubiquitin-like modifier （SUMO） proteases 1 （SENP1） in NSCLC tissues and its role in the regulation of vascular endothelial growth factor （VEGF） expression.We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.Methods A SENP1 small interfering RNA （siRNA） was constructed and transfected into the NSCLC cells.VEGF gene expression was analyzed by real-time polymerase chain reaction （RT-PCR）.Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues.Inhibition of SENP1 by siRNA was associated with decreased VEGF expression.SENP1 was over-expressed in 55 of the 100 NSCLC samples （55％） and was associated with a moderate and low histological tumor grade （3.6％,38.2％,and 58.2％ in high,moderate and low differentiated tumors,respectively,P=0.046）,higher T stage （10.9％ in T1,and 89.1％ in T2 and T3 tumor samples,P ＜0.001）and TNM stage （10.9％ in stage Ⅰ,and 89.1％ in stages Ⅱ and Ⅲ tumor samples,P ＜0.001）.The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group （76.4％） than that in the SENP1 low expression group （33.3％,P ＜0.001）.Sixty three patients received postoperative chemotherapy,including 34 with SENP1 over-expression and 29 with SENP1 low expression.Among the 34 patients with SENP1 over-expression,22 （64.7％） patients developed recurrence or metastasis,significantly higher than those in the low expression group 27.6％ （8/29） （P=0.005）.Multivariate Cox regression analysis showed that lymph node metastasis （P=0.015）,TNM stage （P=-0.001）,and SENP1 expression level （P=0.002） were independent prognostic factors for the survival of NSCLC patients.Conclusions SENP1 may be a promising predictor of survival,a predictive factor of chemo-sensitivity for NSCLC patients,and potentially a desirable drug target for lung carcinoma target therapy.

Expression of SIRT1 signaling pathway in intestinal tissues of neonatal necrotizing enterocolitis

Objective:To analyze the expression of sirtuin type 1 (SIRT1) signal pathway in intestinal tissues of neonatal necrotizing enterocolitis (NEC), and to preliminarily explore the role of SIRT1 in the occurrence of NEC.Methods: From January 2017 to June 2017, the ileal tissues of 35 neonates with NEC underwent one-stage fistula treatment were selected as NEC group, and the ileal tissues of these 35 neonates underwent two-stage fistula treatment were selected as control group. The expression levels of SIRT1, transcription factor-nuclear factor (NF-κB), and SUMO specific protease 1 (SENP1) were detected by qRT-PCR;the expressions of SIRT1, NF-κB, and SENP1 were detected by immunohistochemistry and Western blotting (WB). Results: SIRT1 mRNA, protein positive expression rate, average optical density, and relative protein expression in intestinal tissues of children in NEC group were significantly lower than those in control group (P<0.05), however, the expression of NF-κB, the SENP1 mRNA and protein positive expression rates, the average optical density, and relative protein expression were significantly increased (P<0.05).Conclusion: SIRT1 is low expressed in intestinal tissues of children with NEC, the possible reason is that SIRT1 signaling pathway is suppressed and then NEC occurs.

蛋白质SUMO化修饰与疾病

SUMO(small ubiquitin-related modifier)化修饰作为一种可逆的蛋白质翻译后修饰,从发现至今已有20余年。细胞内被确认能发生SUMO化修饰的蛋白质已超过3 000种。SUMO化修饰能够调控蛋白质的活性,从而影响细胞内诸多生命活动过程,参与了对细胞生理与病理过程的调控。该综述在简要介绍蛋白质SUMO化修饰的基础上,将重点介绍蛋白质SUMO化修饰在疾病发生发展中的相关作用。