口腔鳞状细胞癌预后相关的长链非编码RNA筛选及验证  

Screening and Validation of Long Non-coding RNAs Associated with Prognosis of Oral Squamous Cell Carcinoma

作　　者：刘絮影 李锦存 翟堃[3] 胡晨 董文 马坚 LIU Xuying;LI Jincun;ZHAI Kun;HU Chen;DONG Wen;MA Jian(School of Stomatology,Ningxia Medical University,Yinchuan 750004,China;Department of Stomatology,Nanxishan Hospital of Guangxi Zhuang Autonomous Region,Guilin 541002,China;Department of Oral and Maxillofacial Surgery,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Craniomaxillofacial Deformity Research,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学口腔医学院,宁夏银川750004 [2]广西壮族自治区南溪山医院口腔科,广西桂林541002 [3]宁夏医科大学总医院口腔颌面外科,宁夏银川750004 [4]宁夏颅颌面畸形研究重点实验室,宁夏银川750004

出　　处：《口腔医学研究》2025年第2期109-117,共9页Journal of Oral Science Research

基　　金：宁夏回族自治区自然科学基金(编号:2020AAC03413、2022AAC03473);宁夏回族自治区教育厅高等学校科学研究项目资助(编号:NYG2024155);宁夏医科大学口腔医学院一流学科二期建设(编号:0019110104)。

摘　　要：目的:基于口腔癌在线数据库鉴定与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)预后相关的长链非编码RNA(long non-coding RNA,lncRNA)和mRNA,构建ceRNA网络,分析其在OSCC发生发展中的作用。方法:从癌症基因组图谱(the cancer genome atlas program,TCGA)和基因表达综合数据库(gene expression omnibus database,GEO)中筛选出TCGA-OSCC、GSE23558和GSE30784数据集,进行表达谱分析,筛选出差异表达lncRNA和mRNA,并进行生存分析、基因本体论(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,确定其与OSCC预后的相关性。利用starBase、miRTarBase数据库预测关键lncRNA及mRNA的共同靶标miRNA,以此构建竞争性内源性RNA(competing endogenous RNA,ceRNA)网络。通过实时荧光定量聚合酶链反应(real-time quantitative PCR,qRT-PCR)检测这些关键lncRNA在OSCC细胞系和肿瘤组织中表达水平。结果:表达谱分析鉴定出23个差异表达lncRNA,其中有6个lncRNA与OSCC患者预后相关;mRNA的表达分析鉴定出282个差异表达mRNA,主要富集在三磷酸鸟苷(guanosine triphosphate,GTP)酶激活剂活性、核苷酸结合寡聚化域(nucletide-binding oligomerization domain,NOD)样受体等信号通路,其中10个差异表达的mRNA与OSCC预后相关。ceRNA网络构建了包括6个lncRNA、10个mRNA和靶向预测的26个miRNA分子网络。qRT-PCR结果显示包含LINC01980在内的5个lncRNA在OSCC细胞中高表达,而MIR99AHG低表达。在OSCC组织中,LINC01980表达水平明显升高,而MIR99AHG表达水平降低。结论:本研究筛选的LINC01980和MIR99AHG与OSCC进展和预后相关,可作为OSCC的生物学标志物进一步探讨。Objective:To identify lncRNA and mRNA related to the prognosis of oral squamous cell carcinoma(OSCC)based on the oral cancer online database,construct a ceRNA network,and analyze its role in the occurrence and development of OSCC.Methods:The Cancer Genome Atlas Program(TCGA)and Gene Expression Omnibus database(GEO)were screened from the TCGA-OSCC,GSE23558,and GSE30784 datasets,and the expression profiling was carried out to screen out differentially expressed long non-coding RNA(lncRNAs)and mRNAs.And survival analysis,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to determine the correlation of them with OSCC prognosis.The starBase and miRTarBase databases were used to predict the common target miRNAs of key lncRNAs and mRNAs,so as to construct the competing endogenous RNA(ceRNA)network.Real-time quantitative PCR(qRT-PCR)was used to detect the expression levels of these key lncRNAs in OSCC cell lines and tumor tissues.Results:Expression profiling analysis identified 23 differentially expressed lncRNAs,of which 6 lncRNAs were associated with the prognosis of OSCC patients.The expression analysis of mRNA identified 282 differentially expressed mRNAs,which were mainly enriched in GTPase activator activity,NOD-like receptor,and other signaling pathways,and 10 differentially expressed mRNAs were associated with OSCC prognosis.The ceRNA network consisted of 6 lncRNAs,10 mRNAs,and 26 miRNA molecules for target prediction.The qRT-PCR results showed that 5 lncRNAs,including LINC01980,were highly expressed in OSCC cells,while MIR99AHG was low-expressed.In OSCC tissues,the expression level of LINC01980 was significantly increased,while the expression level of MIR99AHG decreased.Conclusion:The LINC01980 and MIR99AHG screened in this study are related to the progression and prognosis of OSCC,and can be used as biomarkers for further exploration of OSCC.

关 键 词：口腔鳞状细胞癌 长链非编码RNA 预后 LINC01980 MIR99AHG 

分 类 号：R73[医药卫生—肿瘤]