cyclin B1对头颈部鳞状细胞癌生物学特性及细胞焦亡的影响  

Impacts of cyclin B1 on the biological characteristics and pyroptosis of head and neck squamous cell carcinoma

作　　者：罗水妹 张琦 黄谊强 谢贤和[1,2] LUO Shuimei;ZHANG Qi;HUANG Yiqiang;XIE Xianhe(Department of Oncology,Molecular Oncology Research Institute,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China;Fujian Key Laboratory of Precision Medicine for Cancer,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院肿瘤内科,福建医科大学分子肿瘤研究所,福州350005 [2]福建省癌症精准医学重点实验室,福州350005

出　　处：《中国医科大学学报》2022年第3期209-215,共7页Journal of China Medical University

基　　金：福建省自然科学基金(2019J01457)。

摘　　要：目的通过大数据挖掘与实验相结合,探讨cyclin B1表达对头颈部鳞状细胞癌(HNSC)生物学特性及细胞焦亡的影响。方法从GEO、UALCAN及Human Protein Atlas数据库分析cyclin B1在HNSC组织及正常组织的表达及其与临床特征及预后的关系;通过GEO、OncoLnc及GEPAI数据库筛选差异表达及与cyclin B1表达相关的细胞焦亡基因。通过转录组测序、蛋白印迹、ELISA等方法探讨cyclin B1对细胞焦亡的影响。结果UALCAN及GEO数据库分析提示cyclin B1表达在HNSC组织中显著上调(P<0.0001),与不良组织分级、分期及无病生存期(DFS)相关(P<0.05)。HNSC组织中27.27%(9/33)细胞焦亡基因与cyclin B1表达水平相关(P<0.05)。以鼻咽癌CNE-2、HONE-1细胞株为对象的研究显示,与对照组相比,沉默cyclin B1表达可显著增加caspase 1的mRNA表达(P<0.05),增加具有焦亡形态的细胞(P<0.05),增加白细胞介素-1β释放(P>0.05)。蛋白印迹实验结果提示2组焦亡通路关键蛋白caspase 1、caspase 3、GSDMD、GSDME的裂解片段未见显著差异。结论cyclin B1在HNSC组织中呈显著高表达,与HNSC的不良分级、分期及DFS显著相关。cyclin B1表达可能与细胞焦亡生物学过程相关,其分子机制有待进一步研究。Objective To investigate the impacts of cyclin B1 expression on the biological characteristics and pyroptosis of head and neck squamous cell carcinoma(HNSC)by combining database mining and experimental approaches.Methods The expression of cyclin B1 in HNSC and normal tissues,and its relationship with clinical features and prognosis,were analyzed using the GEO,UALCAN,and HPA databases.The differentially expressed and cyclin B1-correlated pyroptosis genes were screened against the GEO,OncoLnc,and GEPAI databases.Transcriptome sequencing,Western blotting analysis,and ELISA were used to investigate the effect of cyclin B1 on pyroptosis.Results Analysis of the UALCAN and GEO databases indicated that cyclin B1 expression was significantly up-regulated in HNSC tissues(P<0.0001),which correlated with the adverse grade,advanced stage,and poorer disease-free survival(DFS)(P<0.05).27.27%(9/33)of the pyroptosis genes were correlated with cyclin B1 expression in HNSC tissue(P<0.05).The study of the nasopharyngeal carcinoma cell lines(CNE-2 and HONE-1)indicated that,compared with the control group,the silencing of cyclin B1 expression significantly increased caspase 1 transcription(P<0.05),pyroptosis-morphology cells(P<0.05),and the release of IL-1β(P>0.05).Western blotting showed that there was no significant difference in the cleavage of caspase 1,caspase 3,GSDMD,and GSDME between the two groups.Conclusion Cyclin B1 is significantly overexpressed in HNSC tissues,which is significantly correlated with the adverse grade,advanced stage,and poorer DFS.Cyclin B1 may be correlated with the biological process of pyroptosis,but its molecular mechanism requires further study.

关 键 词：细胞焦亡 头颈部鳞状细胞癌 cyclin B1 

分 类 号：R739.6[医药卫生—肿瘤]