■肝细胞癌(HCC)在全球范围内继续危害人类健康。竞争内源性RNA(ceRNA)的调控网络在HCC中起重要作用。TP53是HCC中第二最常改变的基因,并且在调节靶基因如miRNA和lncRNA中具有重要作用。
■通过cBioPortal数据库收集来自TP53突变患者的数据,并进行差异分析以筛选与TP53突变相关的RNA。通过miRcode预测lncRNA-miRNA-mRNA关系,miRDB,和TargetScan数据库。通过Cytoscape筛选和可视化ceRNA网络。核心ceRNA网络通过差异分析生成,共表达分析,预后分析和亚细胞定位。最后,甲基化,突变,PPI,GSEA,我们对MEX3A进行了免疫和药物敏感性分析,以确定MEX3A在HCC中的作用.
■我们鉴定了1508个DMRNAs,85个DEmiRNAs和931个DElncRNAs,获得了一个包含28个lncRNAs的ceRNA网络,4个miRNA和31个mRNA。通过Cytoscape筛选出TP53改变相关ceRNA网络中的20个hubDERNA,并通过多重分析获得核心ceRNA网络(LINC00491/TCL6-hsa-miR-139-5p-MEX3A)。此外,我们发现在HCC中MEX3A的甲基化水平降低,突变频率升高.此外,MEX3A表达升高与HCC免疫微环境的改变相关.
■我们成功构建了一个ceRNA互易网络,这为探索肝癌的发病机制和治疗途径提供了新的思路。
UNASSIGNED: Hepatocellular carcinoma (HCC) continues to endanger human health worldwide. Regulatory networks of competing endogenous RNAs (ceRNAs) play important roles in HCC. TP53 is the second most often altered gene in HCC and has a significant role in regulating target genes such as miRNAs and lncRNAs.
UNASSIGNED: Data from patients with TP53 mutation were collected through the cBioPortal database and differential analysis was performed to screen RNAs related to TP53 mutation. The lncRNA-miRNA-mRNA relationship was predicted by the miRcode, miRDB, and TargetScan databases. The ceRNA networks were screened and visualized by Cytoscape. Core ceRNA networks were generated by differential analysis, coexpression analysis, prognostic analysis and subcellular localization. Finally, methylation, mutation, PPI, GSEA, immunity and drug sensitivity analyses of MEX3A were performed to determine the role of MEX3A in HCC.
UNASSIGNED: We identified 1508 DEmRNAs, 85 DEmiRNAs and 931 DElncRNAs and obtained a ceRNA network including 28 lncRNAs, 4 miRNAs and 31 mRNAs. Twenty hub DERNAs in the TP53-altered-related ceRNA network were screened out by Cytoscape and the core ceRNA network (LINC00491/TCL6-hsa-miR-139-5p-MEX3A) was obtained by multiple analyses. In addition, we discovered that the methylation level of MEX3A was decreased and the mutation frequency was raised in HCC. Furthermore, elevated MEX3A expression was associated with alterations in the HCC immunological microenvironment.
UNASSIGNED: We successfully constructed a reciprocal ceRNA network, which could provide new ideas for exploring HCC mechanisms and therapeutic approaches.