Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers
- Yumeng Wang1,
- Xiaoyan Xu2,
- Shuangxing Yu2,
- Kang Jin Kang2,
- Zhicheng Zhou2,
- Leng Han3,
- Yiu Huen Tsang1,
- Jun Li2,
- Hu Chen1,
- Lingegowda S Mangala2,
- Yuan Yuan2,
- A Karina Eterovic2,
- Yiling Lu2,
- Anil K Sood2,
- Kenneth L Scott1,
- Gordon B Mills2 and
- Han Liang2,4
- 1 Baylor College of Medicine;
- 2 The University of Texas MD Anderson Cancer Center;
- 3 The University of Texas Health Science Center at Houston Medical School
- ↵* Corresponding author; email: hliang1{at}mdanderson.org
Abstract
RNA editing, a widespread posttranscriptional 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 8,595 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 that pattern for the wild-type miR-200b expression. We further experimentally demonstrated 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 biomarkers for cancer prognosis and therapy.
- Received December 15, 2016.
- Accepted April 11, 2017.
- Published by Cold Spring Harbor Laboratory Press
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