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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inosine / genetics
  • Proteomics / methods*
  • RNA Editing*
  • Sequence Analysis, RNA
  • Tandem Mass Spectrometry

Substances

  • Inosine
  • Adenosine