C 013: PROMISES & CHALLENGES OF MICRORNAS IN MULTIPLE MYELOMA THERAPY

J Pharm Pharmacogn Res 2(Suppl. 1): S30, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 013: PROMISES & CHALLENGES OF MICRORNAS IN MULTIPLE MYELOMA THERAPY

Palagani A1, Stefan Naulaerts2, Ken Op de Beeck3, Vandesompele J4, Mestdagh F4, Guy Van Camp3, Kris Laukens2,Vanden Berghe W.1

1Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling,2Department of Mathematics and Computer Science,3Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Belgium.
4Center for Medical Genetics, Ghent University, Belgium.
Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy and is the second most common hematological cancer. It is characterized by complex, recurrent genetic and epigenetic abnormalities. Perturbed transcription of various noncoding miRNAs has been demonstrated in MM and their functional roles in MM pathogenesis and therapy response just starts to be unraveled. miRNAs are about 20 nucleotide, single strand, non-coding RNAs that may act as tumor suppressors or oncogenes and regulate gene expression by mRNA degradation or translational repression of hundreds of genes, often in a tissue-specific manner. As such, miRNA dysregulation can have profound cellular consequences. Whereas the loss of tumour-suppressive miRNAs enhances the expression of target oncogenes, increased expression of oncogenic miRNAs (known as oncomirs) can repress target tumour suppressor genes. This creates complex networks regulating a large variety of cellular processes, including differentiation, development, apoptosis and cell cycle progression. Understanding the molecular biology of myeloma also requires linking the miRNome to genomic, transcriptomic, epigenomic and proteomic features of malignant plasma cells. Integrative analysis based on computational target prediction, quantitative proteomics and miRNA/mRNA profiling revealed various functional miRNA-target regulatory networks supported by expression data. We will discuss convergence of microRNA regulation and nuclear factor-κB (NF-κB) and glucocorticoid pathways in MM therapy response. As such, interfering with microRNAs in myeloma regulatory networks holds promise to overcome drug resistance, which may improve clinical outcome.