头颈部鳞癌中FOXP3基因相关的竞争性内源性RNA网络分析

FOXP3-related ceRNA network analysis in head and neck squamous cell carcinoma

目的探索FOXP3基因在头颈部鳞癌中的作用机制。方法选取TCGA数据库中的279例头颈部鳞癌二代测序样本,利用cbioportal筛选样本中FOXP3的共表达基因;利用String数据库,建立FOXP3的共表达网络;利用DAVID数据库分析共表达网络功能;利用miRTar Base和Star Base数据库,筛选能够调控FOXP3的短链非编码RNA(microRNA)、长链非编码RNA(lncRNA)和环状非编码RNA(circRNA);最后,利用Cytoscape软件建立FOXP3的竞争性内源性RNA(ceRNA)网络。结果在TCGA数据库的头颈部鳞癌样本中共筛选出FOXP3的共表达基因950个。(Spearman分数大于0.5)功能分析结果显示这些共表达基因的功能主要为免疫应答,T细胞、淋巴细胞和粒细胞激活等免疫相关功能。ceRNA网络揭示miR-31-5p和miR-210-3p能够靶向调控FOXP3基因。此外,XIST、TUG1、JRK和LINC00473等42个lncRNA和ZNF223_hsa_circ_000898和ISY1_hsa_circ_001090等31个circRNA能够通过ceRNA作用调控FOXP3。结论成功建立FOXP3基因相关的ceRNA网络,并挖掘出42个lncRNA和31个circRNA可能通过ceRNA作用调控FOXP3,可为头颈部鳞状细胞癌的分子机制研究和分子靶向治疗提供新的切入点。

Objective To explore the FOXP3-related mechanism underlying head and neck squamous cell carcinoma. Methods We used cbioportal to identify the co-expressed genes of FOXP3 in 279 samples from head and neck squamous cell carcinoma in TCGA database.We used String database to establish the co-expression network of FOXP3. The function of co-expression network was identified through DAVID database. We used miRTar Base and Star Base database to screen the microRNA,lncRNA and circRNA that regulate FOXP3. Finally,Cytoscape software was used to establish FOXP3-related ceRNA network. Results We found 950 FOXP3 related co-expressed gene.( Spearman score over 0. 5) These genes were enriched in immune response including T cell,leukocyte and lymphocyte activation. CeRNA network revealed that 2 microRNAs( i. e.,miR-31-5p and miR-210-3p),42 lncRNAs( e. g.,XIST,TUG1,JRK and LINC00473) and 31 circRNAs( e. g.,ZNF223_hsa_circ_000898 and ISY1_hsa_circ_001090) could regulate FOXP3. Conclusion We established FOXP3-related ceRNA network and identified 42 lncRNAs and 31 circRNAs that regulate FOXP3. The data generated from this study could provide a new cut point in research and treatment of head and neck squamous cell carcinoma.