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Genes 2016, 7(10), 84; doi:10.3390/genes7100084

Identification of Long Non‐Coding RNAs Deregulated in Multiple Myeloma Cells Resistant to Proteasome Inhibitors

1
Division of Hematology and Oncology, University Hospitals, Case Medical Center, Seidman Cancer Center, Cleveland, OH 44106, USA
2
Department of Pediatrics, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
3
Division of Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
4
The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
*
Author to whom correspondence should be addressed.
Received: 5 July 2016 / Accepted: 27 September 2016 / Published: 6 October 2016
(This article belongs to the Special Issue microRNAs and Other Non-Coding RNAs in Human Diseases)
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Abstract

While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose‐limiting toxicities and the inevitable emergence of drug resistance limit their long‐term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy‐induced, which accounts for the majority of tumor relapses and MM‐related deaths. Non‐coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non‐coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance. While lncRNAs have recently attracted significant attention as therapeutic targets to potentially improve cancer treatment, identification of lncRNAs that are deregulated in cells resistant to PIs has not been previously addressed. We have modeled drug resistance by generating three MM cell lines with acquired resistance to either bortezomib, carfilzomib, or ixazomib. Genome‐wide profiling identified lncRNAs that were significantly deregulated in all three PIresistant cell lines relative to the drug‐sensitive parental cell line. Strikingly, certain lncRNAs deregulated in the three PI‐resistant cell lines were also deregulated in MM plasma cells isolated from newly diagnosed patients compared to healthy plasma cells. Taken together, these preliminary studies strongly suggest that lncRNAs represent potential therapeutic targets to prevent or overcome drug resistance. More investigations are ongoing to expand these initial studies in a greater number of MM patients to better define lncRNAs signatures that contribute to PI resistance in MM. View Full-Text
Keywords: long non‐coding RNA; multiple myeloma; myelomagenesis; proteasome; drug resistance long non‐coding RNA; multiple myeloma; myelomagenesis; proteasome; drug resistance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Malek, E.; Kim, B.; Driscoll, J.J. Identification of Long Non‐Coding RNAs Deregulated in Multiple Myeloma Cells Resistant to Proteasome Inhibitors. Genes 2016, 7, 84.

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