SENP1调控CCNE1参与结肠癌的增殖、侵袭和成瘤能力  

SENP1 involves in proliferation, invasion, and tumorigenesis of colon cancer cells via CCNE1

作　　者：黄河 王磊 巴音达拉[1] 郑广涛 文西年 HUANG He;WANG Lei;Bayindala;ZHENG Guangtao;WEN Xinian(Department of Gastrointestinal Surgery,Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第五附属医院胃肠外科,乌鲁木齐830054

出　　处：《山西医科大学学报》2022年第3期279-286,共8页Journal of Shanxi Medical University

基　　金：新疆维吾尔自治区自然科学基金资助项目(2019D01C270)。

摘　　要：目的 探讨SENP1/CCNE1在结肠癌发生发展中的作用。方法 选取2018年6月至2019年6月新疆医科大学第五附属医院收治的32例结肠癌患者,采用RT-qPCR和Western blot检测患者结肠癌组织和相应癌旁组织中SENP1和CCNE1的表达。首先使用Pearson相关系数法分析SENP1和CCNE1 mRNA的表达相关性,通过Kaplan-Meier法分析SENP1表达与结肠癌患者总生存期(OS)和无病生存期(DFS)的关系。进一步采用RT-qPCR和Western blot方法检测正常肠道细胞HIEC和结肠癌细胞SW480中SENP1的表达,将SW480细胞分为sh-NC组和sh-SENP1组,观察沉默SENP1对SW480细胞中CCNE1蛋白表达水平的影响,分别采用CCK-8法、流式细胞术和Transwell检测沉默SENP1对SW480细胞细胞增殖能力、细胞周期和细胞侵袭能力的影响。最后将裸鼠随机分为sh-NC组和sh-SENP1组,每组6只,观察结肠癌细胞体内成瘤能力。结果 与癌旁组织相比,结肠癌组织中SENP1和CCNE1 mRNA以及蛋白均呈高表达(P<0.05),且SENP1与CCNE1的表达呈正相关(r=0.401 7,P=0.022 7)。与正常肠道细胞HIEC相比,结肠癌细胞SW480中SENP1 mRNA和蛋白呈高表达(P<0.01)。SENP1高表达组患者OS和DFS均明显低于SENP1低表达组(χ^(2)=11.272,P=0.001;χ^(2)=5.575,P=0.018)。与sh-NC组相比,sh-SENP1组细胞中CCNE1的表达降低(t=19.282,P<0.01),并且细胞周期停滞(t=9.520,P<0.01),细胞增殖缓慢(t=13.499,P<0.05),细胞侵袭能力降低(t=15.839,P<0.05)。裸鼠成瘤实验结果显示,沉默SENP1后成瘤能力降低。结论 SENP1通过促进CCNE1的表达,促进结肠癌细胞增殖和细胞周期进展及体内成瘤能力,最终促进结肠癌的发生。Objective To explore the role of SENP1/CCNE1 in the tumourigenesis and development of colon cancer. Methods A total of 32 patients with colon cancer treated in the Fifth Affiliated Hospital of Xinjiang Medical University from June 2018 to June 2019 were selected. The expression levels of SENP1 and CCNE1 in colon cancer tissues and corresponding adjacent tissues were detected by RT-qPCR and Western blot. Pearson correlation coefficient method was used to analyze the correlation between the mRNA expression of SENP1 and CCNE1. Kaplan-Meier method was used to analyze the relationships between SENP1 expression and overall survival(OS) or disease-free survival(DFS) in patients with colon cancer. The expression of SENP1 in HIEC cells and SW480 cells was detected by RT-qPCR and Western blot. SW480 cells were divided into sh-NC group and sh-SENP1 group, and the effect of SENP1 silencing on CCNE1 protein expression was detected by Western blot. CCK-8, flow cytometry and Transwell were used to evaluate the effects of SENP1 silencing on the proliferation, the cell cycle and the invasion capacity of SW480 cells. Nude mice were randomly divided into sh-NC group and sh-SENP1 group to observe in vivo the tumourigenic capacity of SW480 cells, with 6 mice in each group. Results Compared with adjacent tissues, the mRNA and protein levels of CCNE1 and SENP1 were increased in colon cancer tissues(P<0.05). There was a positive correlation between the expression of SENP1 and CCNE1(r=0.401 7,P=0.022 7). Compared with HIEC cells, SENP1 mRNA and protein levels were significantly increased in SW480 cells(P<0.01). OS and DFS in SENP1 high expression group were significantly lower than those in SENP1 low expression group(χ^(2)=11.272,P=0.001;χ^(2)=5.575,P=0.018). Compared with sh-NC group, the expression of CCNE1 in SW480 cells was reduced in sh-SENP1 group(t=19.282,P<0.01). Compared with sh-NC group, the cell cycle of SW480 cells was arrested in sh-SENP1 group(t=9.520,P<0.01), the proliferation was decreased(t=13.499,P<0.01), and the inva

关 键 词：结肠癌 SW480细胞 SENP1 CCNE1 

分 类 号：R735.3[医药卫生—肿瘤]