NEK7通过激活NLRP3炎性小体促进乳腺癌细胞增殖  

NEK7 promotes breast cancer cells proliferation by inducing NLRP3 inflammasome

作　　者：贺婷婷 滕伟峰 贝宴屏 童晶涛 王冠男 杨少辉[5] He Tingting;Teng Weifeng;Bei Yanping;Tong Jingtao;Wang Guannan;Yang Shaohui(Department of Rehabilitation,Li Huili Hospital of Ningbo Medical Center,Ningbo 315000,China;Department of Thyroid and Breast,Li Huili Hospital of Ningbo Medical Center,Ningbo 315000,China;Department of Radiotherapy,Li Huili Hospital of Ningbo Medical Center,Ningbo 315000,China;Department of Hemodialysis Room,Li Huili Hospital of Ningbo Medical Center,Ningbo 315000,China;The 4th Department of Surgery,Li Huili Hospital of Ningbo Medical Center,Ningbo 315000,China)

机构地区：[1]宁波市医疗中心李惠利医院康复全科,315000 [2]宁波市医疗中心李惠利医院甲状腺乳腺外科,315000 [3]宁波市医疗中心李惠利医院放疗科,315000 [4]宁波市医疗中心李惠利医院血透室,315000 [5]宁波市医疗中心李惠利医院外四科,315000

出　　处：《中华内分泌外科杂志》2021年第2期112-116,共5页Chinese Journal of Endocrine Surgery

基　　金：宁波市自然科学基金(2019A610332,2019A610334)。

摘　　要：目的探讨NEK7在乳腺癌中的促癌作用及其潜在的作用机制。方法qPCR法检测NEK7在乳腺癌组织和细胞中的表达,CCK-8法检测NEK7对乳腺癌细胞增殖的影响。生物学数据库筛查可与NEK7相互作用的蛋白,过表达NLRP3观察乳腺癌细胞增殖活性,在乳腺癌细胞中过表达NEK7,Western blot检测NLRP3蛋白表达水平,ELISA检测IL-1β和IL-18表达水平。结果NEK7在乳腺癌组织和细胞中过表达并可促进乳腺癌细胞增殖[NEK7过表达组:24 h为(0.33±0.02)、48 h为(0.59±0.02)、72 h为(0.76±0.02);空白对照组:24 h为(0.30±0.02)、48 h为(0.45±0.02)、72 h为(0.62±0.03);NEK7空载组:24 h为(0.32±0.02)、48 h为(0.46±0.02)、72 h为(0.63±0.03)]。NEK7与NLRP3表达呈正相关(R=0.13),过表达NLRP3可增强乳腺癌细胞增殖活性[NLRP3过表达组:24 h为(0.35±0.02)、48 h为(0.65±0.02)、72 h为(0.80±0.03);空白对照组:24 h为(0.33±0.02)、48 h为(0.51±0.02)、72 h为(0.66±0.03);NLRP3空载组:24 h为(0.34±0.02)、48 h为(0.52±0.03)、72 h为(0.66±0.03)]。NEK7可正调控NLRP3蛋白表达,及上调IL-1β[NEK7过表达组(129.96±7.62)pg/ml,空白对照组(19.80±2.42)pg/ml,NEK7空载组(21.30±1.77)pg/ml]和IL-18[NEK7过表达组(144.08±17.20)pg/ml,空白对照组(16.84±2.34)pg/ml,NEK7空载组(17.64±1.94)pg/ml]表达水平。结论高表达的NEK7通过激活NLRP3炎性小体参与乳腺癌发生发展,显示NEK7可作为乳腺癌治疗的潜在作用靶点。Objective To investigate the role of NIMA-related kinase-7(NEK7)in breast cancer(BC)and its potential molecular mechanism.Methods Quantitative real-time reverse-transcription(RT-qPCR)was used to detect the expression of NEK7 in BC tissue and cell lines.The effect of NEK7 on BC cell proliferation was examined by CCK-8.Proteins interacted with NEK7 were screened in Biological database.The effect of overexpression of NOD-like receptor protein 3(NLRP3)on BC cell proliferation was evaluated.Western blot was used to detect NLRP3 protein expression,and ELISA was employed to evaluate IL-1βand IL-18 expression level.Result NEK7 was upregulated in BC tissues and cells,and enforced-expression of NEK7 promoted BC cell proliferation[NEK7 over-expression group:24 h:(0.33±0.02),48 h:(0.59±0.02),72 h:(0.76±0.02);Blank group:24 h:(0.30±0.02),48 h:(0.45±0.02),72 h:(0.62±0.03);NEK7 empty vector group:24 h:(0.32±0.02),48 h:(0.46±0.02),72 h:(0.63±0.03)].There was a positive correlation between NEK7 and NLRP3(R=0.13).Overexpression of NLRP3 increased the proliferation ability of BC cell[NLRP3 over-expression group:24 h:(0.35±0.02),48 h:(0.65±0.02),72 h:(0.80±0.03);Blank group:24 h:(0.33±0.02),48 h:(0.51±0.02),72 h:(0.66±0.03);NLRP3 empty vector group:24 h:(0.34±0.02),48 h:(0.52±0.03),72 h:(0.66±0.03)].NEK7 could positively regulate NLRP3 protein and up-regulate IL-1β(NEK7 over-expression group:129.96±7.62 pg/ml,Blank group:19.80±2.42pg/ml,NEK7 empty vector group:21.30±1.77 pg/ml)and IL-18(NEK7 over-expression group:144.08±17.20 pg/ml,Blank group:16.84±2.34pg/ml,NEK7 empty vector group:17.64±1.94 pg/ml)expression.Conclusion The upregulation of NEK7 was involved in the process of BC progression by inducing NLRP3 inflammasome activation,suggesting that NEK7 might be a promising therapeutic target for BC.

关 键 词：乳腺癌 NIMA相关激酶7 炎性小体 

分 类 号：R655.8[医药卫生—外科学] R737.9[医药卫生—临床医学]