Abstract
The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an essential aspect of the investigation, which may contribute to understanding the disease's complex pathobiology, providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the clinical relevance of the lncRNA MIAT in MM, taking advantage of the publicly available CoMMpass database. MIAT expression in MM is highly heterogeneous and significantly associated with specific molecular lesions frequently occurring in MM. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of MIAT in different signaling pathways and ribosome biogenesis and assembly. These findings suggest that MIAT deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and, indirectly, the translational process. Although MIAT expression levels seem not to be significantly associated with clinical outcome in multivariate analyses, high MIAT expression levels are associated with bortezomib resistance, this suggesting that MIAT targeting could overcome drug resistance in MM. These findings strongly prompt for further studies investigating the significance of MIAT in MM.
Highlights
Multiple Myeloma (MM) is a malignant proliferation of bone marrow plasma cells (PCs) characterized by a broad clinical spectrum ranging from the pre-malignant condition called monoclonal gammopathy of undetermined significance (MGUS) to extra-medullary myeloma/plasma cell leukemia (PCL) [1]
We have previously identified long non-coding RNAs (lncRNAs) myocardial infarction-associated transcript (MIAT) in a proprietary MM dataset profiled by microarrays, as one of the most significantly down-regulated lncRNAs in patients carrying the t(11;14) in comparison to all others [18]
When we compared the MIAT expression levels of the four healthy donors, 50 MM and 21 PCL cases included in our dataset, we observed a similar low median value in all the groups, heterogeneous expression levels were evidenced in tumor samples, mainly in MM group (Supplementary Figure S1)
Summary
Multiple Myeloma (MM) is a malignant proliferation of bone marrow plasma cells (PCs) characterized by a broad clinical spectrum ranging from the pre-malignant condition called monoclonal gammopathy of undetermined significance (MGUS) to extra-medullary myeloma/plasma cell leukemia (PCL) [1]. Mutations affecting several genes, such as KRAS, NRAS, TP53, BRAF, TRAF3, FAM46C, and DIS3, have been identified and extensively characterized [4,5,6,7,8,9,10] Overall, these events may have a profound impact on the biology and clinical outcome of the disease. These studies have been of high relevance to understand altered molecular pathways in the disease and identify novel prognostic and predictive biomarkers and putative therapeutic targets [2,11,12]. LncRNAs are critical drivers of tumorigenesis by promoting all hallmarks of cancer [16]
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