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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
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Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance

Xu Zhou1, Ramkrishna Mitra2, Fei Hou1

  • 1Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 13, 2023
PubMed

Insights

Adenosine-to-inosine RNA editing influences cancer drug response. This study identifies key RNA editing sites linked to drug resistance, revealing regulatory mechanisms and potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Adenosine-to-inosine RNA editing plays a crucial role in cancer therapy response.
  • Mechanisms by which RNA editing mediates anticancer drug resistance are not fully understood.

Purpose of the Study:

  • To comprehensively identify RNA editing events associated with drug resistance.
  • To elucidate the regulatory mechanisms of RNA editing in mediating anticancer drug resistance.

Main Methods:

  • Identification of 7157 differential editing sites (DESs) from 98,127 informative RNA editing sites in tumor tissues.
  • Validation of DESs in cancer cell lines and investigation of RNA-binding protein regulation.
  • Analysis of DES enrichment in 3'-untranslated regions (3'-UTRs) and impact on microRNA (miRNA) regulation.

Main Results:

  • Diverse editing patterns of DESs were observed in resistant samples, not fully explained by adenosine deaminase acting on RNA.
  • DESs were significantly enriched in 3'-UTRs, impacting miRNA regulation and identifying potential resistance-contributing triplets (DES, miRNA, gene).
  • Genes with DESs were functionally associated with drug resistance pathways, including apoptosis, drug metabolism, and DNA repair.

Conclusions:

  • This study reveals the landscape of RNA editing in drug resistance and its potential regulatory mechanisms.
  • Identified DESs and their regulatory roles offer novel therapeutic targets for overcoming drug resistance.
  • An online resource (http://www.jianglab.cn/REDR/) was developed for accessing DES data.
Keywords:
RNA editingRNA-binding proteinsdrug resistancemicroRNA regulationstherapeutic targets

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