舌鳞状细胞癌中lncRNA相关竞争性内源性RNA网络的综合分析
Comprehensive analysis of lncRNA-associated competing endogenous RNA network in tongue squamous cell carcinoma.
作者信息
Zhang Shusen, Cao Ruoyan, Li Qiulan, Yao Mianfeng, Chen Yu, Zhou Hongbo
机构信息
Department of Prosthodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, China.
Department of Stomatology, Hunan University of Medicine, Hunan, China.
出版信息
PeerJ. 2019 Feb 6;7:e6397. doi: 10.7717/peerj.6397. eCollection 2019.
BACKGROUND
Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the understanding of the ceRNA network in tongue squamous cell carcinoma (TSCC) remains limited.
METHODS
Expression profile data regarding mRNAs, miRNAs and lncRNAs as well as clinical information on 122 TSCC tissues and 15 normal controls from The Cancer Genome Atlas (TCGA) database were collected. We used the edgR package to identify differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) between TSCC samples and normal samples. In order to explore the functions of DEmRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Subsequently, a ceRNA network was established based on the identified DElncRNAs-DEmiRNAs and DEmiRNAs-DEmRNAs interactions. The RNAs within the ceRNA network were analyzed for their correlation with overall disease survival. Finally, lncRNAs were specifically analyzed for their correlation with clinical features in the included TSCC patient samples.
RESULTS
A total of 1867 mRNAs, 828 lncRNAs and 81 miRNAs were identified as differentially expressed in TSCC tissues (-log fold change- ≥ 2; adjusted value <0.01). The resulting ceRNA network included 16 mRNAs, 56 lncRNAs and 6 miRNAs. Ten out of the 56 lncRNAs were found to be associated with the overall survival in TSCC patients ( < 0.05); 10 lncRNAs were correlated with TSCC progression ( < 0.05).
CONCLUSION
Our study deepens the understanding of ceRNA network regulatory mechanisms in TSCC. Furthermore, we identified ten lncRNAs (PART1, LINC00261, AL163952.1, C2orf48, FAM87A, LINC00052, LINC00472, STEAP3-AS1, TSPEAR-AS1 and ERVH48-1) as novel, potential prognostic biomarkers and therapeutic targets for TSCC.
背景
越来越多的证据表明，长链非编码RNA（lncRNAs）在竞争性内源性RNA（ceRNA）网络中发挥重要作用，即它们通过充当微小RNA（miRNAs）的海绵来调节蛋白质编码基因的表达。然而，对于舌鳞状细胞癌（TSCC）中ceRNA网络的了解仍然有限。
方法
收集来自癌症基因组图谱（TCGA）数据库的122例TSCC组织和15例正常对照的mRNA、miRNA和lncRNA的表达谱数据以及临床信息。我们使用edgeR软件包来鉴定TSCC样本和正常样本之间差异表达的mRNA（DEmRNAs）、lncRNA（DElncRNAs）和miRNA（DEmiRNAs）。为了探索DEmRNAs的功能，进行了京都基因与基因组百科全书（KEGG）通路分析。随后，基于鉴定出的DElncRNAs - DEmiRNAs和DEmiRNAs - DEmRNAs相互作用建立ceRNA网络。分析ceRNA网络中的RNA与总体疾病生存率的相关性。最后，特别分析lncRNAs与纳入的TSCC患者样本临床特征的相关性。
结果
共鉴定出1867个mRNA、828个lncRNA和81个miRNA在TSCC组织中差异表达（-log倍数变化≥2；校正P值<0.01）。所得的ceRNA网络包括16个mRNA、56个lncRNA和6个miRNA。发现56个lncRNA中的10个与TSCC患者的总体生存率相关（P<0.05）；10个lncRNA与TSCC进展相关（P<0.05）。
结论
我们的研究加深了对TSCC中ceRNA网络调控机制的理解。此外，我们鉴定出10个lncRNA（PART1、LINC00261、AL163952.1、C2orf48、FAM87A、LINC00052、LINC00472、STEAP3 - AS1、TSPEAR - AS1和ERVH48 - 1）作为TSCC新的潜在预后生物标志物和治疗靶点。
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