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      MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review

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          Abstract

          Early studies have shown how aberrantly expressed microRNAs are a hallmark of several diseases like cancer. MicroRNA expression profiling was shown to be associated with tumour development, progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. Moreover, based on the increasing number of studies demonstrating that microRNAs can function as potential oncogenes or oncosuppressor genes, with the goal to improve disease response and increase cure rates, miRNA-based anticancer therapies have recently been exploited, either alone or in combination with current targeted therapies. The advantage of using microRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. Here, we review our current knowledge about the involvement of microRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.

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          Most cited references 196

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          The hallmarks of cancer.

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            Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.

            We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.
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              MicroRNA expression profiles classify human cancers.

              Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.
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                Author and article information

                Journal
                EMBO Mol Med
                EMBO Mol Med
                emmm
                EMBO Molecular Medicine
                WILEY-VCH Verlag (Weinheim )
                1757-4676
                1757-4684
                March 2012
                : 4
                : 3
                : 143-159
                Affiliations
                [1 ]simpleStart Up Unit, Department of Experimental Oncology, Fondazione IRCCS, Istituto Nazionale Tumori Milano, Italy
                [2 ]simpleDepartment of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University Columbus, OH, USA
                Author notes
                * Corresponding author: Tel: +1 614 292 3063; Fax: +1 614 292 4080; E-mail: carlo.croce@ 123456osumc.edu
                Article
                10.1002/emmm.201100209
                3376845
                22351564
                Copyright © 2012 EMBO Molecular Medicine
                Categories
                Review

                Molecular medicine

                biomarkers, therapeutic impact, diagnostics, human cancer, micrornas

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