TY - JOUR
T1 - Deep sequencing analysis reveals distinctive non-coding RNAs when comparing tumor multidrug-resistant cells and extracellular vesicles with drug-sensitive counterparts
AU - Sousa, Diana
AU - Matthiesen, Rune
AU - Lima, Raquel T.
AU - Helena Vasconcelos, M.
N1 - This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was partially financed by the FEDER - Fundo Europeu de
Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e
a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work is also a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020),
Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a
Tecnologia (FCT). The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of DS (SFRH/BD/98054/2013).
PY - 2020
Y1 - 2020
N2 - Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-eux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, di erent 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.
AB - Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-eux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, di erent 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.
KW - Cancer
KW - Extracellular vesicles
KW - MicroRNAs
KW - Multidrug resistance
KW - Next generation sequencing
KW - Pseudogenes
KW - Small RNAs
UR - http://www.scopus.com/inward/record.url?scp=85079196794&partnerID=8YFLogxK
U2 - 10.3390/cancers12010200
DO - 10.3390/cancers12010200
M3 - Article
C2 - 31947507
AN - SCOPUS:85079196794
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 1
M1 - 200
ER -