title: The HOX gene network in hepatocellular carcinoma.
abstract: Liver organogenesis and cancerogenesis share common mechanisms. HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Less is known about the involvement of HOX genes with liver cancerogenesis. The comparison of the HOX gene network expression between nontumorous livers and hepatocellular carcinomas (HCCs) highlights significant differences in the locus A HOX genes, located on chromosome 7, with a consistent overexpression of HOXA13 mRNA thus validating this gene deregulation as a feature of HCC. HOXA13 is a determinant of gut primordia and posterior body structures. Transcriptome analysis of HCC/nontumorous liver mRNAs, selected on the basis of HOXA13 overexpression, recognizes a set of deregulated genes. The matching of these genes with previously reported HCC transcriptome analysis identifies cell-cycle and nuclear pore-related HCC phenotype displaying poor prognosis. HOXA13 and HOXA7 homeoproteins share a consensus sequence that physically links eIF4E nuclear bodies acting on the export of specific mRNAs (c-myc, FGF-2, vascular endothelial growth factor (VEGF), ornithine decarboxylase (ODC) and cyclin D1). We report the protein-protein interaction between HOXA13 and eIF4E in liver cancer cells and the deregulation of eIF4E mRNA and protein in cell cycle/nuclear pore HCC group phenotype and in T4 stage HCCs, respectively. Thus, transcriptional and post-transcriptional HOXA13 deregulation is involved in HCC possibly through the mRNA nuclear export of eIF4E-dependent transcripts.
authors.affiliation: Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy. clecillo@unina.it
authors.forename: Clemente
authors.initials: C
authors.lastname: Cillo
authors.forename: Giulia
authors.initials: G
authors.lastname: Schiavo
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.forename: Michel P
authors.initials: MP
authors.lastname: Bihl
authors.forename: Paolo
authors.initials: P
authors.lastname: Sorrentino
authors.forename: Vincenza
authors.initials: V
authors.lastname: Carafa
authors.forename: Maria
authors.initials: M
authors.lastname: D' Armiento
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sansano
authors.forename: Raffaela
authors.initials: R
authors.lastname: Vecchione
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E; C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; C099959:homeobox protein HOXA13