早发性结直肠癌发生和转移的免疫相关ceRNA

Immune-associated ceRNA in the development and metastasis of early-onset colorectal cancer

[目的]探讨早发性结直肠癌(EOCRC)发生和转移过程中免疫相关的竞争性内源性RNA(ceRNA)。[方法]下载TCGA数据库中EOCRC的RNA-seq数据,通过差异表达、IMMPORT在线工具、Kaplan-Meier生存曲线和功能富集分析,分别构建肿瘤发生、转移及预后的免疫相关ceRNA调控网络,得到关键基因和通路。[结果]92例EOCRC肿瘤组织和正常组织有差异表达的127个lncRNA、35个miRNA、25个免疫相关mRNA,构建肿瘤发生的免疫相关ceRNA网络,MOCODE1起着重要作用,该网络主要富集在MAPK信号通路,通过生存分析分别构建预后、转移ceRNA网络,发现HCFC1-AS1—hsa-miR-145-5p—PDGFD是共有的调节轴,也是MOCODE1的主要组成,在肿瘤发生、转移过程中,该轴发生了由低到高的表达变化。[结论]HCFC1-AS1—hsa-miR-145-5p—PDGFD轴是EOCRC发生的关键ceRNA,其表达下调,通过MAPK信号通路,促进肿瘤发生,HCFC1-AS1和hsa-miR-145-5p上调与转移(P=3.711e-02&2.682e-02)和不良预后(P=2.578e-02&1.233e-02)相关,PDGFD是潜在的药物靶点。

[Objective]To investigate immune-associated competitive endogenous RNA(ceRNA)in the development and metastasis of early-onset colorectal cancer(EOCRC).[Method] The RNA-seq data of EOCRC was downloaded from the TCGA database,and the immune-related ceRNA networks for tumor occurrence,metastasis and prognosis were constructed after differential expression analysis,IMMPORT online tool,Kaplan-Meier survival curve and functional enrichment analysis,respectively.Therefore,hub genes and pathways were obtained.[Result]There were 127 lncRNAs,35 miRNAs and 25 immune-related mRNAs differentially expressed in 92 cases of EOCRC between tumor tissues and normal tissues.MOCODE1 played an important role in constructing the immune-related ceRNA network of tumorigenesis,which was mainly concentrated in MAPK signaling pathway.Survival analysis was used to construct prognostic and metastatic ceRNA networks respectively.It was found that HCFC1-AS1-hsa-miR-145-5p-PDGFD was a co-regulation axis and a major component of MOCODE1.The expression of this axis changed from low to high during tumorigenicity to metastasis.[Conclusion]The HCFC1-AS1-hsa-miR-145-5p-PDGFD axis was the hub ceRNA in the occurrence of EOCRC.It's down-regulated expression promoted tumorigenesis through MAPK signaling pathway.Upregulation of HCFC1-AS1 and hsa-miR-145-5p was associated with metastasis(P=3.71le-02&2.682e-02)and poor prognosis(P=2.578e-02&1.233e-02),and PDGFD was a potential drug therapeutic target.