Deep sequencing analysis reveals distinctive non-coding RNAs when comparing tumor multidrug-resistant cells and extracellular vesicles with drug-sensitive counterparts

Diana Sousa, Rune Matthiesen, Raquel T. Lima, M. Helena Vasconcelos

Research output: Contribution to journalArticle

2 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number200
JournalCancers
Volume12
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Cancer
  • Extracellular vesicles
  • MicroRNAs
  • Multidrug resistance
  • Next generation sequencing
  • Pseudogenes
  • Small RNAs

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