Construction of Common Differential miRNA Regulatory Network of Hepatocellular Carcinoma and Cholangiocarcinoma and Prediction Analysis of Related Traditional Chinese Medicine Based on Integrated Pharmacology and Transcriptomics
OBJECTIVE:To construct the common differential miRNA regulatory network for hepatocellular carcinoma and cholangiocarcinoma based on integrated pharmacology and transcriptomics,and to perform traditional Chinese medicine prediction analysis on the key targets.METHODS:The hepatocellular carcinoma and cholangiocarcinoma chip datasets were obtained from the GEO database.The differentially expressed miRNA(DEMs)were analyzed and intersected to obtain the common DEMs with the online analysis tool GEO2R.The software of FunRich and miRNet were used to predict upstream transcription factors and downstream target genes.Gene ontology analysis(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of target genes were performed by using DAVID database.STRING database and Cytoscape 3.9.1 software were used to screen key genes(hubGenes)and construct miRNA-hubGenes network.UALCAN,Kaplan Meier-plotter and Coremin Medical databases were used to analyze the differential expression of key genes,overall survival rate and related traditional Chinese medicine prediction analysis.RESULTS:Totally 14 DEMs were screened from hepatocellular carcinoma,and 104 DEMs were screened from cholangiocarcinoma.miR-199a-5p was the common DEMs of the two,involving 28 up-regulated transcription factors and 166 downstream target genes.Enrichment analysis showed that these target genes were involved in the biological processes of tumor cell apoptosis,proliferation,mesenchymal transition and migration,mainly through the cancer pathway,FoxO signaling pathway,mitogen-activated protein kinase signaling pathway and PI3K-Akt signaling pathway.The core target associated with the medicinal taste was slightly cold,mainly attributed to the liver channel,and the most closely associated Chinese medicine was Radix Salviae.CONCLUSIONS:miR-199a-5p is an important regulatory miRNA between hepatocellular carcinoma and cholangiocarcinoma,and the occurrence of key genes of Radix Salviae intervention is more frequent,which is basically consistent with the research reports,and provides basis and reference for the subsequent mechanism research and clinical application of hepatobiliary carcinoma.
Hepatocelluar carcinomaCholangiocarcinomamiRNATraditional Chinese medicine predictionTranscriptomics