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      Anabolic Androgenic Steroids: Searching New Molecular Biomarkers

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          Abstract

          Even if anabolic androgenic steroid (AAS) abuse is clearly associated with a wide spectrum of collateral effects, adolescents and athletes frequently use a large group of synthetic derivatives of testosterone, both for aesthetic uses and for improving performance. Over the last few years, the development of MicroRNA (miRNA) technologies has become an essential part of research projects and their role as potential molecular biomarkers is being investigated by the scientific community. The circulating miRNAs detection as a diagnostic or prognostic tool for the diagnosis and treatment of several diseases is very useful, because with a minimal quantity of sample (peripheral blood), miRNAs are very sensitive. Even more, miRNAs remain stable both at room temperature and during freeze-thaw cycles. These characteristics highlight the important role of miRNAs in the near future as new tools for anti-doping. The article provides a systematic review and meta-analysis on the role of miRNAs as new potential molecular biomarkers of AAS use/abuse. Particularly, this paper analyzed the “miRNA signature” use as biomarkers for health disorders, focusing on the organ damages which are related to ASS use/abuse. Moreover, this review aims to provide a future prospect for less invasive or non-invasive procedures for the detection of circulating miRNA biomarkers as doping assumption signaling.

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          Most cited references103

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          The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2.

          MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K(+) channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.
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            A cellular microRNA mediates antiviral defense in human cells.

            In eukaryotes, 21- to 24-nucleotide-long RNAs engage in sequence-specific interactions that inhibit gene expression by RNA silencing. This process has regulatory roles involving microRNAs and, in plants and insects, it also forms the basis of a defense mechanism directed by small interfering RNAs that derive from replicative or integrated viral genomes. We show that a cellular microRNA effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (PFV-1) in human cells. PFV-1 also encodes a protein, Tas, that suppresses microRNA-directed functions in mammalian cells and displays cross-kingdom antisilencing activities. Therefore, through fortuitous recognition of foreign nucleic acids, cellular microRNAs have direct antiviral effects in addition to their regulatory functions.
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              MicroRNA signature predicts survival and relapse in lung cancer.

              We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                20 November 2018
                2018
                : 9
                : 1321
                Affiliations
                [1] 1Department of Clinical and Experimental Medicine, University of Foggia , Foggia, Italy
                [2] 2Department of Legal, Historical, Economic and Social Sciences, University of Catanzaro , Catanzaro, Italy
                [3] 3Medical and Surgical Sciences, University of Catanzaro , Catanzaro, Italy
                [4] 4Department of Medical, Surgical and Advanced Technologies “G.F. Ingrassia”, University of Catania , Catania, Italy
                Author notes

                Edited by: Filippo Caraci, Università degli Studi di Catania, Italy

                Reviewed by: Robert Nistico, Università della Calabria, Italy; Gianluigi Mazzoccoli, Casa Sollievo della Sofferenza (IRCCS), Italy

                *Correspondence: Francesco Sessa francesco.sessa@ 123456unifg.it

                This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.01321
                6256094
                30524281
                56afe9b8-2f3c-465d-a9c0-5dda67410612
                Copyright © 2018 Sessa, Salerno, Di Mizio, Bertozzi, Messina, Tomaiuolo, Pisanelli, Maglietta, Ricci and Pomara.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 September 2018
                : 29 October 2018
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 129, Pages: 12, Words: 8663
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                anabolic androgenic steroids (aass),adverse effects,mirnas,doping,new molecular biomarkers

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