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| Status |
Public on Sep 17, 2020 |
| Title |
RNA editing in cancer impacts mRNA abundance in immune response pathways |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNA editing generates modifications to 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. Here, we carry out integrative analysis of RNA editing profiles between epithelial (E) and mesenchymal (M) tumors, since epithelial-mesenchymal transition (EMT) is a key paradigm for metastasis. We identify distinct editing patterns between E and M tumors in seven cancer types using TCGA data, an observation further supported by single-cell RNA-seq data and ADAR perturbation experiments in cell culture. Through computational analyses and experimental validations, we show that differential editing sites between E and M phenotypes function by regulating mRNA abundance of their respective genes. Our analysis of >120 RNA-binding proteins revealed ILF3 as a potential regulator of this process, supported by experimental validations. Consistent with the known roles of ILF3 in immune response, E-M 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. Our 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.
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| Overall design |
eCLIP-seq in A549 cells.
RNA-seq in A549 cells upon knockdown of ADARs.
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| Contributor(s) |
Chan T, Fu T, Bahn JH, Jun H, Lee J, Quinones-Valdez G, Cheng C, Xiao X |
| Citation(s) |
33106178 |
| Submission date |
Mar 24, 2020 |
| Last update date |
Nov 02, 2020 |
| Contact name |
Xinshu Xiao |
| E-mail(s) |
gxxiao@g.ucla.edu
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| Organization name |
University of California, Los Angeles
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| Street address |
610 Charles E. Young Drive S
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095-1570 |
| Country |
USA |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (15)
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| GSM4735052 |
A549 cells, A12si1 |
| GSM4735053 |
A549 cells, A12si2 |
| GSM4735054 |
A549 cells, A12si3 |
| GSM4735055 |
A549 cells, A1si1 |
| GSM4735056 |
A549 cells, A1si2 |
| GSM4735057 |
A549 cells, A1si3 |
| GSM4735058 |
A549 cells, A2si1 |
| GSM4735059 |
A549 cells, A2si2 |
| GSM4735060 |
A549 cells, A2si3 |
| GSM4735061 |
A549 cells, con1 |
| GSM4735062 |
A549 cells, con2 |
| GSM4735063 |
A549 cells, con3 |
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| Relations |
| BioProject |
PRJNA614963 |
| SRA |
SRP253895 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147487_ILF3_A549.both_reps_and_alu.gene_annotated.alu_annotated.bed.gz |
1.4 Mb |
(ftp)(http) |
BED |
| GSE147487_siADARs_A549.TPM.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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