Oncotarget

Research Papers:

HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape

Mariarosaria Conte, Carmela Dell’Aversana, Rosaria Benedetti, Francesca Petraglia, Annamaria Carissimo, Valeria Belsito Petrizzi, Alfonso Maria D’Arco, Ciro Abbondanza, Angela Nebbioso and Lucia Altucci _

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Oncotarget. 2015; 6:886-901. https://doi.org/10.18632/oncotarget.2816

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Abstract

Mariarosaria Conte1, Carmela Dell’Aversana2, Rosaria Benedetti1, Francesca Petraglia1, Annamaria Carissimo1, Valeria Belsito Petrizzi3, Alfonso Maria D’Arco3, Ciro Abbondanza1, Angela Nebbioso1 and Lucia Altucci1,2

1 Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT

2 Institute of Genetics and Biophysics, IGB ‘Adriano Buzzati-Traverso’, Via P. Castellino, Naples, IT

3 Division of Onco-Hematology, Umberto I Hospital, via S. Francesco, Nocera Inferiore (SA), IT

Correspondence:

Lucia Altucci, email:

Keywords: HDAC2, leukemia, HDAC inhibitors, MHC class II

Received: July 30, 2014 Accepted: November 24, 2014 Published: November 25, 2014

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.


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