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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11709-11739
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11709
Non-coding landscapes of colorectal cancer
Marco Ragusa, Cristina Barbagallo, Luisa Statello, Angelo Giuseppe Condorelli, Rosalia Battaglia, Lucia Tamburello, Davide Barbagallo, Cinzia Di Pietro, Michele Purrello
Marco Ragusa, Cristina Barbagallo, Luisa Statello, Angelo Giuseppe Condorelli, Rosalia Battaglia, Lucia Tamburello, Davide Barbagallo, Cinzia Di Pietro, Michele Purrello, BioMolecular, Genome and Complex Systems BioMedicine Unit (BMGS) - Section of Biology and Genetics G Sichel, Department of BioMedical Sciences and BioTechnology, University of Catania, 95123 Catania, Italy
Author contributions: All authors analyzed the literature and wrote the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marco Ragusa, PhD, BioMolecular, Genome and Complex Systems BioMedicine Unit (BMGS) - Section of Biology and Genetics G Sichel, Department of BioMedical Sciences and BioTechnology, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy. mragusa@unict.it
Telephone: +39-095-3782089 Fax: +39-095-3782073
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: June 23, 2015
Revised: July 28, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 7, 2015
Processing time: 158 Days and 18.7 Hours
Abstract

For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy.

Keywords: Colorectal cancer; MicroRNA; Long non-coding RNAs; Circular RNAs; Diagnosis; Prognosis; Therapy

Core tip: For many decades the predominant view of molecular functioning of organisms stated that proteins represent the main regulators of genomes and their dysfunctions were the first cause of diseases. This protein-centred view was too simplistic to explain the complexity of cancer. In the last few years many studies have revealed that about 85% of our genome is pervasively transcribed, mainly as non-protein-coding RNAs (ncRNAs). The discovery of countless molecular alterations of ncRNAs related to cancer changed the paradigms of cancer biology. In this review, we report recent advances in the discovery of ncRNAs involved in Colorectal Cancer pathobiologies, and their potential applications in diagnosis, prognosis and therapy.