Identification And Analysis Of P53-mediated Competing Endogenous RNA Network In Human Hepatocellular Carcinoma And Construction Of TF Mediated Enhancer-RNA Database

Recent studies have indicated that long non-coding RNAs(IncRNAs)and mRNAs function as competing endogenous RNAs(ceRNAs)that compete to bind to shared microRNA(miRNA)recognition elements(MREs)to perform specific biological functions during tumorigenesis.The tumor suppressor p53 is a master regulator of cancer-related biological processes by acting as a transcription factor to regulate target genes including miRNA and IncRNA.However,the mechanism in human hepatocellular carcinoma and whether p53-mediated RNA targets could form ceRNA network remain unclear.Here,we identified a series of differential expressed miRNAs,IncRNAs and mRNAs which were potentially regulated by p53 using RNA sequencing in HepG2.Genomic characteristics comparative analysis showed significant differences between mRNAs and IncRNAs.By integrating experimentally confirmed Ago2 and p53 binding sites,to elucidate the regulatory relationship between p53-mediated miRNA and mRNA,IncRNA,then we constructed a highly reliable p53-mediated ceRNA network using hypergeometric test.The KEGG pathway enrichment analysis showed that the ceRNA network highly enriched in the cancer or p53-associated signaling pathways.Finally,using betweenness centrality analysis,we identified five master miRNAs(hsa-miR-3620-5p,hsa-miR-3613-3p,hsa-miR-6881-3p,hsa-miR-6087 and hsa-miR-18a-3p)that regulated most of the target RNAs,suggesting these miRNAs play central roles in the whole p53-mediated ceRNAs network.Taken together,our results provide a new regulatory mechanism of p53 networks for future studies in cancer therapeutics.Enhancers are DNA elements that could increase the expression of specific genes.With the intensification of related research,there is an increasing need to elucidate the potential role of enhancers in cellular regulation.Therefore,we developed a specifically designed interactive database EnhancerDB(http://lcbb.swjtu.edu.cn/EnhancerDB),to reveal the pattern among them.EnhancerDB mainly focuses on integrating different elements,including TF,miRNA,mRNA and SNP,to better understand the regulatory network around enhancers and the function of enhancers.A total of 68,592 different enhancers for 41 tissues or cell lines were identified,and 406 TFs,1,727 microRNAs,20,343 genes and 6,920,105 SNPs were also collected into this database.Moreover,EnhancerDB provides a set of user-friendly tools to query the elements of interest,and reveal the other elements associated with it.