A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma.

Aristea-Maria Papanota,Pinelopi I Artemaki,Christine-Ivy Liacos,Maria Gavriatopoulou,Christos K Kontos,Tina Bagratuni,Andreas Scorilas,Paraskevi Karousi,Evangelos Terpos,Meletios-Athanasios Dimopoulos,Margaritis Avgeris,Evangelos Eleutherakis-Papaiakovou,Ioannis Ntanasis-Stathopoulos,Efstathios Kastritis,Panagiotis Malandrakis,Maria-Alexandra Papadimitriou

doi:10.3390/ijms222313144

Abstract

Multiple myeloma (MM) is the second most common hematological malignancy, arising from terminally differentiated B cells, namely plasma cells. miRNAs are small non-coding RNAs that participate in the post-transcriptional regulation of gene expression. In this study, we investigated the role of nine miRNAs in MM. CD138+ plasma cells were selected from bone marrow aspirates from MM and smoldering MM (sMM) patients. Total RNA was extracted and in vitro polyadenylated. Next, first-strand cDNA synthesis was performed using an oligo-dT–adapter primer. For the relative quantification of the investigated miRNAs, an in-house real-time quantitative PCR (qPCR) assay was developed. A functional in silico analysis of the miRNAs was also performed. miR-16-5p and miR-155-5p expression was significantly lower in the CD138+ plasma cells of MM patients than in those of sMM patients. Furthermore, lower levels of miR-15a-5p, miR-16-5p, and miR-222-3p were observed in the CD138+ plasma cells of MM patients with osteolytic bone lesions, compared to those without. miR-125b-5p was also overexpressed in the CD138+ plasma cells of MM patients with bone disease that presented with skeletal-related events (SREs). Furthermore, lower levels of miR-223-3p were associated with significantly worse overall survival in MM patients. In conclusion, we propose a miRNA signature with putative clinical utility in MM.

Highlights

Multiple myeloma (MM) is a neoplasm arising from plasma cells
In order to quantify each miRNA in all the samples, we developed and optimized quantitative PCR (qPCR) assays
MiRNAs are regulatory molecules implicated in the vast majority of biological procedures

Summary

Introduction

Multiple myeloma (MM) is a neoplasm arising from plasma cells. It accounts for1–1.8% of all malignancies and is the second commonest hematological malignancy [1].MM develops in a multistep process, starting from its asymptomatic precursor states: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (sMM). Multiple myeloma (MM) is a neoplasm arising from plasma cells. MM develops in a multistep process, starting from its asymptomatic precursor states: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (sMM). All these disease entities are part of a spectrum of diseases referred to as plasma cell dyscrasias. The major difference between MM and its precursors is that MM is characterized by end-organ damage, triggered by the monoclonal protein and/or the cytokines secreted by malignant plasma cells. The clinical manifestations of the disease are hypercalcemia, anemia, renal impairment, and bone disease [2]

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Conclusion