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      The Role of Bioactive Dietary Components in Modulating miRNA Expression in Colorectal Cancer

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          Abstract

          Colorectal cancer is the third most common cancer in the world and considered to be one of the most diet-related types of cancer. Extensive research has been conducted but still the link between diet and colorectal cancer is complex. Recent studies have highlight microRNAs (miRNAs) as key players in cancer-related pathways in the context of dietary modulation. MicroRNAs are involved in most biological processes related to tumor development and progression; therefore, it is of great interest to understand the underlying mechanisms by which dietary patterns and components influence the expression of these powerful molecules in colorectal cancer. In this review, we discuss relevant dietary patterns in terms of miRNAs modulation in colorectal cancer, as well as bioactive dietary components able to modify gene expression through changes in miRNA expression. Furthermore, we emphasize on protective components such as resveratrol, curcumin, quercetin, α-mangostin, omega-3 fatty acids, vitamin D and dietary fiber, with a focus on the molecular mechanisms in the context of prevention and even treatment. In addition, several bioactive dietary components that have the ability to re-sensitize treatment resistant cells are described.

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          Most cited references112

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          Switching from repression to activation: microRNAs can up-regulate translation.

          AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
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            Nuclear export of microRNA precursors.

            MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
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              Specificity of microRNA target selection in translational repression.

              MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted miRNA:mRNA interactions must be viewed in the context of other potential interactions and cellular conditions.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                26 September 2016
                October 2016
                : 8
                : 10
                : 590
                Affiliations
                [1 ]Department of Bromatology, Hygiene, Nutrition, University of Medicine and Pharmacy “Iuliu Hatieganu”, Marinescu Street 23, Cluj-Napoca 400337, Romania; laura.biris@ 123456umfcluj.ro (L.I.G.); dmiere@ 123456umfcluj.ro (D.M.)
                [2 ]Department of Pharmaceutical Biochemistry and Clinical Laboratory, University of Medicine and Pharmacy “Iuliu Hatieganu”, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania; inaionescu@ 123456yahoo.com
                [3 ]Department of Functional Genomics, Proteomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Republicii Street 34-36, Cluj-Napoca 400015, Romania; oana.tudoran@ 123456iocn.ro
                [4 ]Department of Surgical and Gynecological Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Republicii Street 34-36, Cluj-Napoca 400015, Romania; cosminlisencu@ 123456yahoo.com
                [5 ]Department of Surgery, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Republicii Street 34-36, Cluj-Napoca 400015, Romania
                Author notes
                [* ]Correspondence: ovidiubalacescu@ 123456iocn.ro ; Tel.: +40-264-590-638
                Article
                nutrients-08-00590
                10.3390/nu8100590
                5083978
                27681738
                7e79115a-b754-4798-b4e8-d0d98c651510
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 July 2016
                : 18 September 2016
                Categories
                Review

                Nutrition & Dietetics
                colorectal cancer,microrna,diet,bioactive dietary components
                Nutrition & Dietetics
                colorectal cancer, microrna, diet, bioactive dietary components

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