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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
Summary
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.
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