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

Xinxin Peng, Xiaoyan Xu, Yumeng Wang, David H. Hawke, Shuangxing Yu, Leng Han, Zhicheng Zhou, Kamalika Mojumdar, Kang Jin Jeong, Marilyne Labrie, Yiu Huen Tsang, Minying Zhang, Yiling Lu, Patrick Hwu, Kenneth L. Scott, Han Liang, Gordon B. Mills

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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. By an integrated analysis of TCGA genomic data and CPTAC proteomic data, Peng et al. show that A-to-I RNA editing contributes to proteomic diversity in breast cancer through changes in amino acid sequences. The edited COPA protein increases proliferation, migration, and invasion of cancer cells in vitro.

Original languageEnglish (US)
Pages (from-to)817-828.e7
JournalCancer cell
Volume33
Issue number5
DOIs
StatePublished - May 14 2018

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core
  • Bioinformatics Shared Resource
  • Flow Cytometry and Cellular Imaging Facility
  • Functional Proteomics Reverse Phase Protein Array Core
  • Cytogenetics and Cell Authentication Core
  • Proteomics Facility

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