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Cancer Cell. 2018 May 14;33(5):817-828.e7. doi: 10.1016/j.ccell.2018.03.026. Epub 2018 Apr 26.

A-to-I RNA Editing Contributes to Proteomic Diversity in Cancer.

Author information

1
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province 110122, China.
3
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA.
4
The Proteomics and Metabolomics Facility, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
6
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
7
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
8
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
9
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
10
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
11
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: hliang1@mdanderson.org.

Abstract

Adenosine (A) to inosine (I) RNA editing introduces many nucleotide changes in cancer transcriptomes. However, due to the complexity of post-transcriptional regulation, the contribution of RNA editing to proteomic diversity in human cancers remains unclear. Here, we performed an integrated analysis of TCGA genomic data and CPTAC proteomic data. Despite limited site diversity, we demonstrate that A-to-I RNA editing contributes to proteomic diversity in breast cancer through changes in amino acid sequences. We validate the presence of editing events at both RNA and protein levels. The edited COPA protein increases proliferation, migration, and invasion of cancer cells in vitro. Our study suggests an important contribution of A-to-I RNA editing to protein diversity in cancer and highlights its translational potential.

KEYWORDS:

ADAR enzyme; CPTAC; RNA editing; RNA-seq; TCGA; amino acid changes; biomarker; cancer drivers; mass spectrometry data; somatic mutations

PMID:
29706454
PMCID:
PMC5953833
[Available on 2019-05-14]
DOI:
10.1016/j.ccell.2018.03.026

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