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Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers
- Source :
- Genome research. 27(7)
- Publication Year :
- 2016
-
Abstract
- RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.
- Subjects :
- 0301 basic medicine
Male
Adenosine
Leukemia Inhibitory Factor Receptor alpha Subunit
Leukemia inhibitory factor receptor
Disease
Biology
Cancer prognosis
03 medical and health sciences
Neoplasms
microRNA
Genetics
Humans
Metastasis suppressor
Genes, Tumor Suppressor
Neoplasm Invasiveness
RNA, Neoplasm
Genetics (clinical)
Zinc Finger E-box Binding Homeobox 2
Regulation of gene expression
Research
Zinc Finger E-box-Binding Homeobox 1
Patient survival
Inosine
Neoplasm Proteins
MicroRNAs
030104 developmental biology
RNA editing
Female
RNA Editing
Subjects
Details
- ISSN :
- 15495469
- Volume :
- 27
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Genome research
- Accession number :
- edsair.doi.dedup.....215e09b950d954b3c7d1fe9da90aa4fe