title: Altered RNA editing in 3' UTR perturbs microRNA-mediated regulation of oncogenes and tumor-suppressors.
abstract: RNA editing is a molecular event that alters specific nucleotides in RNA post-transcriptionally. RNA editing has the potential to impact a variety of cellular processes and is implicated in diseases such as cancer. Yet, the precise mechanisms by which RNA editing controls cellular processes are poorly understood. Here, we characterize sequences altered by RNA editing in patient samples from lymphoma, neuroblastoma and head and neck cancers. We show that A-to-I RNA editing sites are highly conserved across samples of the same tissue type and that most editing sites identified in tumors are also detectable in normal tissues. Next, we identify the significant changes in editing levels of known sites between tumor and paired "normal" tissues across 14 cancer types (627 pairs) from The Cancer Genome Atlas project and show that the complexity of RNA editing regulation cannot be captured by the activity of ADAR family genes alone. Our pan-cancer analysis confirms previous results on individual tumor types and suggests that changes of RNA editing levels in coding and 3'UTR regions could be a general mechanism to promote tumor growth. We also propose a model explaining how altered RNA editing levels affect microRNA-mediated post-transcriptional regulation of oncogenes and tumor-suppressors.
authors.affiliation: Computational Biomedicine, Boston University School of Medicine, Boston, 02118, MA, US.
authors.forename: Liye
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, 02118, MA, US.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, 02118, MA, US.
authors.forename: Xaralabos
authors.initials: X
authors.lastname: Varelas
authors.affiliation: Computational Biomedicine, Boston University School of Medicine, Boston, 02118, MA, US.
authors.forename: Stefano
authors.initials: S
authors.lastname: Monti
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009857:Oncogenes; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing; D034622:RNA Interference; D017423:Sequence Analysis, RNA; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2