PT  - JOURNAL ARTICLE
AU  - Tracey Chan
AU  - Ting Fu
AU  - Jae Hoon Bahn
AU  - Hyun-Ik Jun
AU  - Jae-Hyung Lee
AU  - Giovanni Quinones-Valdez
AU  - Chonghui Cheng
AU  - Xinshu Xiao
TI  - Differential RNA editing between epithelial and mesenchymal tumors impacts mRNA abundance in immune response pathways
AID  - 10.1101/2020.03.06.981191
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.06.981191
4099  - http://biorxiv.org/content/early/2020/03/08/2020.03.06.981191.short
4100  - http://biorxiv.org/content/early/2020/03/08/2020.03.06.981191.full
AB  - Recent studies revealed global shifts in RNA editing, the modification of RNA sequences, across many cancers. Besides a few sites implicated in tumorigenesis or metastasis, most tumor-associated sites, predominantly in noncoding regions, have unknown function. Here, we characterize editing profiles between epithelial (E) and mesenchymal (M) phenotypes in seven cancer types, as epithelial-mesenchymal transition (EMT) is a key paradigm for metastasis. We observe distinct editing patterns between E and M tumors and EMT induction upon loss of ADAR enzymes in cultured cells. E-M differential sites are highly enriched in genes involved in immune and viral processes, some of which regulate mRNA abundance of their respective genes. We identify a novel mechanism in which ILF3 preferentially stabilizes edited transcripts. Among editing-dependent ILF3 targets is the transcript encoding PKR, a crucial player in immune response. Our study demonstrates the broad impact of RNA editing in cancer and relevance of editing to cancer-related immune pathways.