MicroRNA editing in seed region aligns with cellular changes in hypoxic conditions

Giovanni Nigita, Mario Acunzo, Giulia Romano, Dario Veneziano, Alessandro Laganà, Marika Vitiello, Dorothee Wernicke, Alfredo Ferro, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

RNA editing is a finely tuned, dynamic mechanism for post-transcriptional gene regulation that has been thoroughly investigated in the last decade. Nevertheless, RNA editing in non-coding RNA, such as microRNA (miRNA), have caused great debate and have called for deeper investigation. Until recently, in fact, inadequate methodologies and experimental contexts have been unable to provide detailed insights for further elucidation of RNA editing affecting miRNAs, especially in cancer. In this work, we leverage on recent innovative bioinformatics approaches applied to a more informative experimental context in order to analyze the variations in miRNA seed region editing activity during a time course of a hypoxia-exposed breast cancer cell line. By investigating its behavior in a dynamic context, we found that miRNA editing events in the seed region are not depended on miRNA expression, unprecedentedly providing insights on the targetome shifts derived from these modifications. This reveals that miRNA editing acts under the influence of environmentally induced stimuli. Our results show a miRNA editing activity trend aligning with cellular pathways closely associated to hypoxia, such as the VEGF and PI3K/Akt pathways, providing important novel insights on this poorly elucidated phenomenon.

Original languageEnglish
Pages (from-to)6298-6308
Number of pages11
JournalNucleic Acids Research
Volume44
Issue number13
DOIs
StatePublished - 27 Jul 2016

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