title: Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. However, present studies of its multiple gene interaction and cellular pathways still could not explain the initiation and development of HCC perfectly. To find the key genes and miRNAs as well as their potential molecular mechanisms in HCC, microarray data GSE22058, GSE25097, and GSE57958 were analyzed.
  
  
  METHODS
  The microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed using the DAVID database, and the protein-protein interaction (PPI) network was constructed using the Cytoscape software. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs).
  
  
  RESULTS
  A total of 115 differentially expressed genes (DEGs) were found in HCC, including 52 up-regulated genes and 63 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses from DAVID showed that up-regulated genes were significantly enriched in chromosome segregation and cell division, while the down-regulated genes were mainly involved in complement activation, protein activation cascades, carboxylic acid metabolic processes, oxoacid metabolic processes, and the immune response. From the PPI network, the 18 nodes with the highest degree were screened as hub genes. Among them, ESR1 was found to have close interactions with FOXO1, CXCL12, and GNAO1. In addition, a total of 64 DEMs were identified, which included 58 up-regulated miRNAs and 6 down-regulated miRNAs. ESR1 was potentially targeted by five miRNAs, including hsa-mir-18a and hsa-mir-221.
  
  
  CONCLUSIONS
  The roles of DEMs like hsa-mir-221 in HCC through interactions with DEGs such as ESR1 and CXCL12 may provide new clues for the diagnosis and treatment of HCC patients.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Mou
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Xufu
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Daofeng
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China. wzjtcy@126.com.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Wu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012984:Software
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger
keywords: Differentially expressed genes; Liver cancer; Microarray analysis; Protein–protein interaction network; miRNA