精子发生和中心粒相关1在头颈鳞癌进展中的作用及其调控机制  

Spermatogenesis and centriole associated 1 promotes the progression of head and neck squamous cell carcinoma in an O-GlcNAcylation-mediated manner

作　　者：戴耀章[1] 张亚民[1] 王刘中[1] 宋瑞鹏[2] Dai Yaozhang;Zhang Yamin;Wang Liuzhong;Song Ruipeng(Department of Throat&Head and Neck Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzou 450052,China;Department of Orthopedics,the First Affiliated Hospital of Zhengzhou University,Zhengzou 450052,China)

机构地区：[1]郑州大学第一附属医院咽喉头颈外科,450052 [2]郑州大学第一附属医院骨科,450052

出　　处：《中华实验外科杂志》2022年第7期1379-1382,共4页Chinese Journal of Experimental Surgery

摘　　要：目的观察精子发生和中心粒相关1(SPATC1)在头颈鳞癌组织及细胞系中的表达,探寻可能的调控机制。方法利用生物信息学技术筛选出SPATC1;用免疫组织化学和蛋白印迹实验分别检测SPATC1在头颈鳞癌组织及细胞中的表达,Kaplan-Meier法分析SPATC1在头颈鳞癌组织表达与患者预后的相关性;使用小干扰RNA(siRNA)下调SPATC1和氧连接乙酰葡萄糖胺转移酶(OGT)的表达,使用外源表达质粒上调SPATC1和OGT的表达,筛选构建稳定的细胞系。采用细胞计数试剂盒(CCK-8)实验和流式细胞术分析分别研究SPATC1和OGT表达水平变化对细胞增殖及凋亡的影响;成对资料采用Student’st检验,多组间比较采用单因素方差分析(组间比较采用LSD-t检验)。使用Pearson相关系数评价OGT基因与SPATC1表达的相关性。结果HNSCC组织及细胞系中的SPTC1表达显著升高(组织0.809±0.438,细胞0.809±0.306,P<0.01),SPATC1高表达组患者的总生存率明显低于SPATC1低表达组(χ2=7.713,P<0.01);细胞转染中,SPATC1表达上调导致细胞增殖明显增加(Fadu细胞和SCC154F=202.006,F=230.678,P均<0.05;LSD-t检验P均<0.05),同时细胞凋亡减少(Fadu细胞和SCC154F=2855.197,F=1130.925,P均<0.05)。而SPATC1下调导致相反的结果(P均<0.05)。OGT mRNA表达水平变化与肿瘤细胞SPATC1 mRNA及蛋白表达水平呈正相关(OGT mRNA与SPATC1 mRNA相关性:Fadur=0.742,SCC154r=0.645;OGT mRNA与SPATC1蛋白相关性:Fadur=0.790,SCC154r=0.687,P<0.05)。结论SPATC1在HNSCC中高表达,可以促进HNSCC肿瘤细胞增殖,减少其凋亡。SPATC1受O-GlcNAc糖基化修饰调控,与OGT关系密切。Objective Bioinformatics analysis showed that spermatogenesis and centriole associated 1(SPATC1)was a candidate oncogene in head and neck squamous cell carcinoma(HNSCC).We aimed to uncover whether SPATC1 is involved in O-GlcNAcylation-mediated HNSCC progression,as well as investigate its underlying mechanism.Methods SPATC1 expression in HNSCC tissues and cells was detected by real-time quantitative polymerase chain reaction(RT-PCR),Western blotting and immunohistochemistry(IHC).Cell proliferation,apoptosis and tumorigenesis were determined by cell counting kit-8(CCK-8),flow cytometry.Results SPATC1 was highly expressed in HNSCC tissues and cells(0.809±0.438 in HNSCC tissues,0.809±0.306 in HNSCC cells,P<0.01),and its high expression was closely related to the shorter overall survival of HNSCC patients(χ2=7.713;Log rank test,P<0.01).In addition,SPATC1 functioned as an oncogene in HNSCC and its expression was positively regulated by O-GlcNAc transferase(OGT).Up-regulation of SPATC1 induced an obvious increase in cell proliferation(Fadu F=202.006,SCC154 F=230.678,P<0.05.LSD-t test P<0.05)and a reduction in cell apoptosis(Fadu F=2855.197,SCC154 F=1130.925,P<0.05.LSD-t test P<0.05).Encouragingly,down-regulation of SPATC1 caused opposite results(P<0.05).The expression of OGT mRNA was positively correlated with the expression of SPATC1 at both mRNA and protein levels(the correlation between OGT mRNA and SPATC1 mRNA:Fadu r=0.742,SCC154 r=0.645;the correlation between OGT mRNA and SPATC1 protein:Fadu r=0.790,SCC154 r=0.687).Conclusion The high expression of SPATC1 in HNSCC tissues and cells is closely associates with the poor prognosis of HNSCC patients.Up-regulation of SPATC1 induced an obvious increase in cell proliferation and a reduction in cell apoptosis.Furthermore,SPATC1 is regulated by O-GlcNAcylation,probably through OGT-mediated manner.

关 键 词：精子发生和中心粒相关1 氧连接乙酰葡萄糖胺糖基化修饰 头颈肿瘤 

分 类 号：R739.91[医药卫生—肿瘤]