Abstract

Simple SummaryAdenosine to inosine (A-to-I) editing is a type of RNA editing where individual adenosines are enzymatically converted into inosines. A-to-I RNA editing plays an important role in cancer biology. Several studies have demonstrated that A-to-I editing of microRNAs (miRNAs) very often affect miRNA function as oncosuppressors or oncogenes, hence showing clinical relevance. Hence, A-to-I miRNA editing has been suggested as a potential diagnostic and prognostic tool in the monitoring of cancer patients. Nevertheless, the process of identifying and characterizing miRNA editing events in tumor samples still presents several challenges. In this review, we outline molecular aspects linked to miRNA A-to-I editing and retrace methods and approaches dedicated to detection of editing sites and functional characterization of edited miRNAs in cancer.Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. The employment of powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

Highlights

  • The presence of various RNA modifications has long been recognized

  • Adenosine to inosine (A-to-I) RNA editing is one of the best-characterized. It consists of the irreversible conversion of adenosine to inosine and is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, ADAR1 and ADAR2

  • ADAR1, which comprises two distinct isoforms, i.e., p110 and p150, is ubiquitously expressed [5]. It is involved in organogenesis, hematopoiesis, and suppression of immune response mediated by double-stranded RNA-activated immunoproteins like the RIG-I-like receptor MDA5 and the interferoninduced PKR (p150 only) [6,7,8]

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Summary

Introduction

The presence of various RNA modifications has long been recognized. only recently, the study of their occurrence and function has received attention [1]. The restoration of ADAR2 editing resulted in the inhibition of tumor cell growth and proliferation both in vitro and in vivo [16,17,18,19] In this regard, an elucidated mechanism concerns the ADAR2-mediated control of the dual-specificity protein phosphatase CDC14B expression. The downregulation of ADAR2 in glioblastomas and astrocytoma causes a significant under-expression of CDC14B, with a consequent unbalance in cell cycle progression [19]. These facts have increasingly prompted the research on A-to-I RNA editing in oncology

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