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RNA editing in cancer impacts mRNA abundance in immune response pathways
- Source :
- Genome Biology, Genome Biology, Vol 21, Iss 1, Pp 1-25 (2020), Genome biology, vol 21, iss 1
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- BackgroundRNA editing generates modifications to the RNA sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in editing levels across many cancer types, as well as a few specific mechanisms implicating individual sites in tumorigenesis or metastasis. However, most tumor-associated sites, predominantly in noncoding regions, have unknown functional relevance.ResultsHere, we carry out integrative analysis of RNA editing profiles between epithelial and mesenchymal tumors, since epithelial-mesenchymal transition is a key paradigm for metastasis. We identify distinct editing patterns between epithelial and mesenchymal tumors in seven cancer types using TCGA data, an observation further supported by single-cell RNA sequencing data and ADAR perturbation experiments in cell culture. Through computational analyses and experimental validations, we show that differential editing sites between epithelial and mesenchymal phenotypes function by regulating mRNA abundance of their respective genes. Our analysis of RNA-binding proteins reveals ILF3 as a potential regulator of this process, supported by experimental validations. Consistent with the known roles of ILF3 in immune response, epithelial-mesenchymal differential editing sites are enriched in genes involved in immune and viral processes. The strongest target of editing-dependent ILF3 regulation is the transcript encoding PKR, a crucial player in immune and viral response.ConclusionsOur study reports widespread differences in RNA editing between epithelial and mesenchymal tumors and a novel mechanism of editing-dependent regulation of mRNA abundance. It reveals the broad impact of RNA editing in cancer and its relevance to cancer-related immune pathways.
- Subjects :
- lcsh:QH426-470
Bioinformatics
Adenosine Deaminase
Carcinogenesis
1.1 Normal biological development and functioning
Messenger
Computational biology
Biology
medicine.disease_cause
Cell Line
Underpinning research
Information and Computing Sciences
Cell Line, Tumor
Neoplasms
Genetics
medicine
2.1 Biological and endogenous factors
Humans
RNA, Messenger
Aetiology
Nuclear Factor 90 Proteins
lcsh:QH301-705.5
Gene
Cancer
Regulation of gene expression
Messenger RNA
Tumor
Sequence Analysis, RNA
Research
Immunity
RNA-Binding Proteins
RNA
Biological Sciences
Phenotype
lcsh:Genetics
lcsh:Biology (General)
Gene Expression Regulation
A549 Cells
RNA editing
Gene Knockdown Techniques
ADAR
RNA Editing
Sequence Analysis
Environmental Sciences
Biotechnology
Subjects
Details
- ISSN :
- 1474760X
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Genome Biology
- Accession number :
- edsair.doi.dedup.....d7197f3b733aff194e64e332deb56279