Factors Regulating microRNA Expression and Function in Multiple Myeloma.

Irena Misiewicz-Krzeminska,Norma Gutiérrez,Patryk Krzeminski,Luis Corchete,Elizabeta Rojas,Dalia Quwaider,Ana Herrero

doi:10.3390/ncrna5010009

Abstract

Intensive research has been undertaken during the last decade to identify the implication of microRNAs (miRNAs) in the pathogenesis of multiple myeloma (MM). The expression profiling of miRNAs in MM has provided relevant information, demonstrating different patterns of miRNA expression depending on the genetic abnormalities of MM and a key role of some miRNAs regulating critical genes associated with MM pathogenesis. However, the underlying causes of abnormal expression of miRNAs in myeloma cells remain mainly elusive. The final expression of the mature miRNAs is subject to multiple regulation mechanisms, such as copy number alterations, CpG methylation or transcription factors, together with impairment in miRNA biogenesis and differences in availability of the mRNA target sequence. In this review, we summarize the available knowledge about the factors involved in the regulation of miRNA expression and functionality in MM.

Highlights

Multiple myeloma (MM) is a neoplasm characterized by the accumulation of clonal plasma cells (PC) in bone marrow, which is generally associated with the production of a monoclonal immunoglobulin and lytic bone lesions
Initial studies of conventional cytogenetics and fluorescent in situ hybridization (FISH), and more advanced studies based on microarrays and new generation sequencing (NGS), have revealed the existence of different types of genetic alterations that can be categorized into translocations, copy number abnormalities (CNAs) and point mutations [2,3,4]
Different functions have been described for miRNAs, the most relevant is the downregulation of gene expression at the post-transcriptional level by targeting specific messenger RNAs, either for degradation when fully paired to the seed region binding site at the 30 untranslated region (30 UTR) of the mRNA target, or for inhibition of translation through partial base-pairing to complementary sites

Summary

Introduction

Multiple myeloma (MM) is a neoplasm characterized by the accumulation of clonal plasma cells (PC) in bone marrow, which is generally associated with the production of a monoclonal immunoglobulin and lytic bone lesions. Different functions have been described for miRNAs, the most relevant is the downregulation of gene expression at the post-transcriptional level by targeting specific messenger RNAs (mRNAs), either for degradation when fully paired to the seed region binding site at the 30 untranslated region (30 UTR) of the mRNA target, or for inhibition of translation through partial base-pairing to complementary sites. MiRNAs are involved in critical biological processes, including cellular growth and differentiation, and can contribute to cancer pathogenesis (reviewed in [10,11,12,13,14]). In this regard, miRNAs have been shown to be deregulated in MM. A comprehensive review of the main mechanisms regulating miRNA expression and function, with focus on data available in MM, will be provided

Copy Number Abnormalities Affect Expression of miRNAs

Transcriptional Regulation of miRNA Expression

Impaired miRNA Processing may Deregulate miRNA Expression

Impact of miRNA–mRNA Associations

Findings

Conclusions