Long Non-Coding RNAs in Multiple Myeloma

Abstract

Multiple myeloma (MM) is an incurable disease caused by the malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Although a large fraction of the genome is actively transcribed, most of the transcripts do not serve as templates for proteins and are referred to as non-coding RNAs (ncRNAs), broadly divided into short and long transcripts on the basis of a 200-nucleotide threshold. Short ncRNAs, especially microRNAs, have crucial roles in virtually all types of cancer, including MM, and have gained importance in cancer diagnosis and prognosis, predicting the response to therapy and, notably, as innovative therapeutic targets. Long ncRNAs (lncRNAs) are a very heterogeneous group, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis, and invasion. LncRNAs are aberrantly expressed in various types of cancers, including hematological malignancies, showing either oncogenic or tumor suppressive functions. However, the mechanisms of the related disease-causing events are not yet revealed in most cases. Besides emerging as key players in cancer initiation and progression, lncRNAs own many interesting features as biomarkers with diagnostic and prognostic importance and, possibly, for their utility in therapeutic terms as druggable molecules. This review focuses on the role of lncRNAs in the pathogenesis of MM and summarizes the recent literature.

Keywords: expression profiling; long non-coding RNAs (lncRNAs); multiple myeloma (MM); transcription regulation.

Figure 1

Oncogenic events, such as the main chromosomal aberrations and gene mutations, through the different stages of plasma cell (PC) dyscrasias are represented. The relative expression level (scaled to common y-axis range on the upper and lower values) of the long ncRNAs (lncRNAs) deregulated through the progressive stages of PC dyscrasias is shown [26]. Abbreviations: NPC = normal plasma cell; MGUS = monoclonal gammopathy of undetermined significance; sMM = smoldering multiple myeloma; MM = multiple myeloma; PCL = plasma cell leukemia.