Next Article in Journal
Recovery of Filtered Graphene Oxide Residue Using Elastic Gel Packed in a Column by Cross Flow
Next Article in Special Issue
The Spectrum of Mechanism-Oriented Models and Methods for Explanations of Biological Phenomena
Previous Article in Journal
Special Issue: Microbial Community Modeling: Prediction of Microbial Interactions and Community Dynamics
Previous Article in Special Issue
FluxVisualizer, a Software to Visualize Fluxes through Metabolic Networks
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessFeature PaperArticle
Processes 2018, 6(5), 42;

ADAR Mediated RNA Editing Modulates MicroRNA Targeting in Human Breast Cancer

Department of Biology, University of South Alabama, Mobile, AL 36688-0002, USA
Department of Pharmacology, USA College of Medicine, Mobile, AL 36688-0002, USA
Author to whom correspondence should be addressed.
Received: 6 April 2018 / Revised: 19 April 2018 / Accepted: 21 April 2018 / Published: 25 April 2018
(This article belongs to the Special Issue Methods in Computational Biology)
PDF [2743 KB, uploaded 3 May 2018]


RNA editing by RNA specific adenosine deaminase acting on RNA (ADAR) is increasingly being found to alter microRNA (miRNA) regulation. Editing of miRNA transcripts can affect their processing, as well as which messenger RNAs (mRNAs) they target. Further, editing of target mRNAs can also affect their complementarity to miRNAs. Notably, ADAR editing is often increased in malignancy with the effect of these RNA changes being largely unclear. In addition, numerous reports have now identified an array of miRNAs that directly contribute to various malignancies although the majority of their targets remain largely undefined. Here we propose that modulating the targets of miRNAs via mRNA editing is a frequent occurrence in cancer and an underappreciated participant in pathology. In order to more accurately characterize the relationship between these two regulatory processes, this study examined RNA editing events within mRNA sequences of two breast cancer cell lines (MCF-7 and MDA-MB-231) and determined whether or not these edits could modulate miRNA associations. Computational analyses of RNA-Seq data from these two cell lines identified over 50,000 recurrent editing sites within human mRNAs, and many of these were located in 3′ untranslated regions (UTRs). When these locations were screened against the list of currently-annotated miRNAs we discovered that editing caused a subset (~9%) to have significant alterations to mRNA complementarity. One miRNA in particular, miR-140-3p, is known to be misexpressed in many breast cancers, and we found that mRNA editing allowed this miRNA to directly target the apoptosis inducing gene DFFA in MCF-7, but not in MDA-MB-231 cells. As these two cell lines are known to have distinct characteristics in terms of morphology, invasiveness and physiological responses, we hypothesized that the differential RNA editing of DFFA in these two cell lines could contribute to their phenotypic differences. Indeed, we confirmed through western blotting that inhibiting miR-140-3p increases expression of the DFFA protein product in MCF-7, but not MDA-MB-231, and further that inhibition of miR-140-3p also increases cellular growth in MCF-7, but not MDA-MB-231. Broadly, these results suggest that the creation of miRNA targets may be an underappreciated function of ADAR and may help further elucidate the role of RNA editing in tumor pathogenicity. View Full-Text
Keywords: ADAR; breast; cancer; inosine; microRNA; microRNA targeting; RNA editing ADAR; breast; cancer; inosine; microRNA; microRNA targeting; RNA editing

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Roberts, J.T.; Patterson, D.G.; King, V.M.; Amin, S.V.; Polska, C.J.; Houserova, D.; Crucello, A.; Barnhill, E.C.; Miller, M.M.; Sherman, T.D.; Borchert, G.M. ADAR Mediated RNA Editing Modulates MicroRNA Targeting in Human Breast Cancer. Processes 2018, 6, 42.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Processes EISSN 2227-9717 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top