microRNA editing in seed region aligns with cellular changes in hypoxic conditions.
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.
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Giovanni
G
Nigita
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA mario.acunzo@osumc.edu.
Mario
M
Acunzo
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Giulia
G
Romano
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Dario
D
Veneziano
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Alessandro
A
Laganà
Department of Clinicaland Molecular Biomedicine, University of Catania, Catania 95125, Italy.
Marika
M
Vitiello
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Dorothee
D
Wernicke
Department of Structural & Functional Biology, University 'Federico II' of Naples, Naples 80126, Italy.
Alfredo
A
Ferro
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA carlo.croce@osumc.edu.
Carlo M
CM
Croce
D001943:Breast Neoplasms / Q000235:genetics*; D015687:Cell Hypoxia / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059647:Gene-Environment Interaction; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt