Comparison of Expression Signature of Histone Deacetylases (HDACs) in Mesenchymal Stem Cells from Multiple Myeloma and Normal Donors

Abstract

BACKGROUND: Histone acetylation in chromatin structures plays a key role in regulation of gene transcription and is strictly controlled by histone acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has been reported in several cancers. MATERIALS AND METHODS: The expression of 10 HDACs (including HDAC class I and II) was studied by quantitative reverse transcriptionPCR (qRTPCR) in a cohort of mesenchymal stem cells (MMMSCs) from 10 multiple myeloma patients with a median age 60y. The results were compared with those obtained for normal donors. Then, a coculture system was performed between MMMSCs and u266 cell line, in the presence or absence of sodium butyrate (NaBT), to understand the effects of HDAC inhibitors (HDACi) in MMMSCs on multiple myeloma cases. Also, the interleukin6 (IL6) and vascular endothelial growth factor (VEGFA) gene expression level and apoptotic effects were investigated in MMMSCs patients and control group following NaBT treatment. RESULTS: The results indicated that upregulated (HDACs) and downregulated (IL6 and VEGFA) genes were differentially expressed in the MMMSCs derived from patients with multiple myeloma and NDMSCs from normal donors. Comparison of the MMMSCs and NDMSCs also showed distinct HDACs expression patterns. For the first time to our knowledge, a significant increase of apoptosis was observed in coculture with MMMSCs treated with NaBT. CONCLUSIONS: The obtained findings elucidate a complex set of actions in MSCs in response to HDAC inhibitors, which may be responsible for anticancer effects. Also, the data support the idea that MSCs are new therapeutic targets as a potential effective strategy for MM.