MMP10促进口腔鳞状细胞癌细胞的增殖、迁移、侵袭及淋巴结转移  

MMP10 promotes the proliferation,migration,invasion and lymph node metastasis of oral squamous cell carcinoma cells

作　　者：曲静 吴晓婷 兰婷 郑大利 卢友光[1] 甘瑞环 丁林灿[1] QU Jing;WU Xiaoting;LAN Ting;ZHENG Dali;LU Youguang;GAN Ruihuan;DING Lincan(Fujian Key Laboratory of Oral Diseases&Fujian Provincial Engineering Research Center of Oral Biomaterial&Stomatological Key lab of Fujian College and University,School and Hospital of Stomatology,Fujian Medical University,Fuzhou 350000,Fujian Province,China)

机构地区：[1]福建省口腔疾病研究重点实验室,福建省口腔生物材料工程技术研究中心,福建省高校口腔医学重点实验室,福建医科大学口腔医学院/附属口腔医院,福建福州350000

出　　处：《肿瘤》2024年第4期380-392,共13页Tumor

基　　金：福建省自然科学基金项目(2022J01761,2022J01270)

摘　　要：目的:研究基质金属蛋白酶10(matrix metalloproteinase 10,MMP10)对口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)细胞增殖、迁移、侵袭及淋巴结转移的影响,并探讨可能的作用机制。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)组织及癌旁组织的基因表达谱数据和生存数据,并从临床蛋白质组学肿瘤分析联盟(Clinical Proteomic Tumor Analysis Consortium,CPTAC)数据库下载HNSCC组织及癌旁组织的蛋白质表达谱数据,并从中筛选出属于OSCC类型的数据。使用上述公共数据库的数据分析HNSCC/OSCC组织和癌旁组织中MMP10在m RNA和蛋白表达水平上的差异,并分析MMP10表达水平对HNSCC患者生存率的影响,以及人类乳头瘤病毒(human papillomavirus,HPV)对HNSCC患者中MMP10基因的表达水平影响。采用实时荧光定量PCR检测52对OSCC组织样本和癌旁组织样本(来自福建医科大学附属第一医院)中MMP10的表达水平。使用si RNA(si MMP10-1291和si MMP10-1336)沉默MMP10的表达后,采用CCK-8法和细胞集落形成实验检测MMP10对OSCC细胞增殖能力的影响,采用细胞划痕愈合实验和Transwell小室实验分别检测MMP10对OSCC细胞迁移和侵袭能力的影响。使用sh RNA(sh MMP10-1291和sh MMP10-1336)构建裸鼠舌癌正位模型,在体内验证敲低MMP10表达水平对OSCC细胞发生淋巴结转移的影响。根据TCGA数据库中OSCC患者的基因表达谱数据筛筛选出与MMP10相关的差异表达基因,并采用软件GSEA进行通路富集分析,进一步分析MMP10与显著富集通路基因之间的相关性。结果:相比于癌旁组织,MMP10在HNSCC和OSCC组织中的表达水平明显升高(P<0.0001),并且MMP10高表达HNSCC患者具有更低的生存率(HR=1.32,P=0.04)。HPV-组HNSCC患者具有更高的MMP10基因表达水平(P<0.0001),但其生存率却明显低于HPV+组HNSCC患者(HR=0.48,P=0.004)。下调MMP10的表达后可以抑制OObjective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent noncancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Comp

关 键 词：口腔鳞状细胞癌 基质金属蛋白酶10 转移 WNT3A 

分 类 号：R739.8[医药卫生—肿瘤]