title: HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape.
abstract: Histone deacetylase 2 (HDAC2) is overexpressed or mutated in several disorders such as hematological cancers, and plays a critical role in transcriptional regulation, cell cycle progression and developmental processes. Here, we performed comparative transcriptome analyses in acute myeloid leukemia to investigate the biological implications of HDAC2 silencing versus its enzymatic inhibition using epigenetic-based drug(s). By gene expression analysis of HDAC2-silenced vs wild-type cells, we found that HDAC2 has a specific role in leukemogenesis. Gene expression profiling of U937 cell line with or without treatment of the well-known HDAC inhibitor vorinostat (SAHA) identifies and characterizes several gene clusters where inhibition of HDAC2 'mimics' its silencing, as well as those where HDAC2 is selectively and exclusively regulated by HDAC2 protein expression levels. These findings may represent an important tool for better understanding the mechanisms underpinning immune regulation, particularly in the study of major histocompatibility complex class II genes.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.affiliation: Institute of Genetics and Biophysics, IGB 'Adriano Buzzati-Traverso', Via P. Castellino, Naples, IT.
authors.forename: Carmela
authors.initials: C
authors.lastname: Dell'Aversana
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Benedetti
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Francesca
authors.initials: F
authors.lastname: Petraglia
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Carissimo
authors.affiliation: Division of Onco-Hematology, Umberto I Hospital, via S. Francesco, Nocera Inferiore (SA), IT.
authors.forename: Valeria Belsito
authors.initials: VB
authors.lastname: Petrizzi
authors.affiliation: Division of Onco-Hematology, Umberto I Hospital, via S. Francesco, Nocera Inferiore (SA), IT.
authors.forename: Alfonso Maria
authors.initials: AM
authors.lastname: D'Arco
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Ciro
authors.initials: C
authors.lastname: Abbondanza
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.Institute of Genetics and Biophysics, IGB 'Adriano Buzzati-Traverso', Via P. Castellino, Naples, IT.|Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT.Institute of Genetics and Biophysics, IGB 'Adriano Buzzati-Traverso', Via P. Castellino, Naples, IT.
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D000208:Acute Disease; D000368:Aged; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D059467:Transcriptome; D020298:U937 Cells; D000077337:Vorinostat
chemical_list: D001549:Benzamides; D006680:HLA Antigens; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011725:Pyridines; C118739:entinostat; D000077337:Vorinostat; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2