Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

Yumeng Wang, Xiaoyan Xu, Shuangxing Yu, Kang Jin Jeong, Zhicheng Zhou, Leng Han, Yiu Huen Tsang, Jun Li, Hu Chen, Lingegowda S. Mangala, Yuan Yuan, A. Karina Eterovic, Yiling Lu, Anil K. Sood, Kenneth L. Scott, Gordon B. Mills, Han Liang

Research output: Contribution to journalArticle

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1112-1125
Number of pages14
JournalGenome Research
Volume27
Issue number7
DOIs
StatePublished - Jul 2017

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Wang, Y., Xu, X., Yu, S., Jeong, K. J., Zhou, Z., Han, L., Tsang, Y. H., Li, J., Chen, H., Mangala, L. S., Yuan, Y., Eterovic, A. K., Lu, Y., Sood, A. K., Scott, K. L., Mills, G. B., & Liang, H. (2017). Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers. Genome Research, 27(7), 1112-1125. https://doi.org/10.1101/gr.219741.116