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Extracellular Vesicles and Cancer: A Focus on Metabolism, Cytokines, and Immunity
Open AccessArticle

Deep Sequencing Analysis Reveals Distinctive Non-Coding RNAs When Comparing Tumor Multidrug-Resistant Cells and Extracellular Vesicles with Drug-Sensitive Counterparts

1
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2
Cancer Drug Resistance Group, IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal
3
Department of Biological Sciences, FFUP—Faculty of Pharmacy of the University of Porto, 4050-313 Porto, Portugal
4
Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
5
Department of Pathology, FMUP—Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
6
Cancer Signalling & Metabolism Group, IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(1), 200; https://doi.org/10.3390/cancers12010200
Received: 26 November 2019 / Revised: 7 January 2020 / Accepted: 9 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Extracellular Vesicles in Cancer Progression and Drug Resistance)
Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-efflux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, different studies have shown that extracellular vesicles (EVs) participate in the communication between MDR cells and drug-sensitive counterparts, promoting dissemination of the MDR phenotype. In the present work, we aimed to identify RNA species present in MDR cells and in EVs released by those cells, which may be associated with the MDR phenotype. The RNA content from two pairs (leukemia and lung cancer) of MDR (P-gp overexpressing) cells and their drug-sensitive counterparts, as well as from their EVs, was analyzed by deep sequencing. Our results showed distinctive transcripts for MDR cells and their EVs, when compared with their drug-sensitive counterparts. Remarkably, two pseudogenes (a novel pseudogene and RNA 5.8S ribosomal pseudogene 2) were found to be increased in EVs released by MDR cells in both leukemia and lung cancer models. Moreover, six miRs (miR-204-5p, miR-139-5p, miR-29c-5p, miR-551b-3p, miR-29b-2-5p, and miR-204-3p) exhibited altered levels in lung cancer MDR cells and their EVs. This study provides insights into the contribution of EVs to MDR. View Full-Text
Keywords: Cancer; multidrug resistance; extracellular vesicles; next generation sequencing; small RNAs; microRNAs; pseudogenes Cancer; multidrug resistance; extracellular vesicles; next generation sequencing; small RNAs; microRNAs; pseudogenes
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Sousa, D.; Matthiesen, R.; Lima, R.T.; Vasconcelos, M.H. Deep Sequencing Analysis Reveals Distinctive Non-Coding RNAs When Comparing Tumor Multidrug-Resistant Cells and Extracellular Vesicles with Drug-Sensitive Counterparts. Cancers 2020, 12, 200.

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