Abstract
Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology.
Highlights
Multiple myeloma (MM) is a malignant proliferation of antibody-secreting bone marrow plasma cells (PCs) characterized by a wide clinical spectrum ranging from the presumed pre-malignant condition called monoclonal gammopathy of undetermined significance (MGUS), to smoldering MM (SMM), truly overt and symptomatic MM, and extra-medullary myeloma/plasma cell leukemia (PCL) [1,2,3]
The expression profiles of long non-coding RNAs (lncRNAs) have been investigated by Gene 1.0 ST array in a large cohort of 268 patients included in two different datasets and representative of the major forms of plasma cell dyscrasia
Our study identified 31 lncRNAs that were deregulated in this pathology compared to normal bone marrow PC controls (Table 1)
Summary
Multiple myeloma (MM) is a malignant proliferation of antibody-secreting bone marrow plasma cells (PCs) characterized by a wide clinical spectrum ranging from the presumed pre-malignant condition called monoclonal gammopathy of undetermined significance (MGUS), to smoldering MM (SMM), truly overt and symptomatic MM, and extra-medullary myeloma/plasma cell leukemia (PCL) [1,2,3]. During the years that have followed human genome sequencing, it has become evident that over 90% of the genome is actively transcribed [5, 6], the majority of transcripts being represented by non-coding RNA (ncRNA) and not translated into proteins. NcRNAs are broadly divided into short (200 nt) transcripts. Dysregulation of short ncRNAs, miRNAs, has been reported to occur virtually in all types of cancer, including MM, highlighting the usefulness of miRNA profiling in diagnosis, prognosis, and in predicting response to therapy [7, 8]. MiRNAs are currently considered both emerging therapeutic targets and innovative intervention tools in cancer including MM [9,10,11]
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