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      Functional Landscape of Dysregulated MicroRNAs in Oral Squamous Cell Carcinoma: Clinical Implications

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          Abstract

          MicroRNA (miRNA) dysregulation is associated with the pathogenesis of oral squamous cell carcinoma (OSCC), and its elucidation could potentially provide information on patient outcome. A growing body of translational research on miRNA biology is focusing on precision oncology, aiming to decode the miRNA regulatory network in the development and progression of cancer. Tissue-specific expression and stable presence in all body fluids are unique features of miRNAs, which could be potentially exploited in the clinical setting. Recent understanding of miRNA properties has led them to be useful, attractive, and potential tools either as biomarkers (distinct miRNA expression signature) for diagnosis and prognostic outcomes or as targets for novel therapeutic entities, enabling personalized treatment for OSCC. In this review, we discuss recent research on different aspects of alterations in miRNA profiles along with their clinical significance and strive to identify probable potential miRNA biomarkers for diagnosis and prognosis of OSCC. We also discuss the current understanding and scope of development of miRNA-based therapeutics against OSCC.

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          Most cited references79

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          Roles for microRNAs in conferring robustness to biological processes.

          Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems. Copyright © 2012 Elsevier Inc. All rights reserved.
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            miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay.

            microRNAs (miRNAs) regulate gene expression through translational repression and/or messenger RNA (mRNA) deadenylation and decay. Because translation, deadenylation, and decay are closely linked processes, it is important to establish their ordering and thus to define the molecular mechanism of silencing. We have investigated the kinetics of these events in miRNA-mediated gene silencing by using a Drosophila S2 cell-based controllable expression system and show that mRNAs with both natural and engineered 3' untranslated regions with miRNA target sites are first subject to translational inhibition, followed by effects on deadenylation and decay. We next used a natural translational elongation stall to show that miRNA-mediated silencing inhibits translation at an early step, potentially translation initiation.
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              Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers.

              The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                12 May 2020
                2020
                : 10
                : 619
                Affiliations
                [1] 1Tata Translational Cancer Research Center, Tata Medical Center , Kolkata, India
                [2] 2Department of Head and Neck Surgical Oncology, Tata Medical Center , Kolkata, India
                [3] 3Saroj Gupta Cancer Centre and Research Institute , Kolkata, India
                Author notes

                Edited by: Jorge A. R. Salvador, University of Coimbra, Portugal

                Reviewed by: Cesare Piazza, Istituto Nazionale dei Tumori (IRCCS), Italy; Agnieszka Sobecka, Poznan University of Medical Sciences, Poland

                This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2020.00619
                7274490
                32547936
                b095b46f-6c5a-4ac8-8446-cbfd670fbf2e
                Copyright © 2020 Ghosh, Pattatheyil and Roychoudhury.

                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
                : 19 September 2019
                : 03 April 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 123, Pages: 11, Words: 9466
                Funding
                Funded by: Department of Health Research 10.13039/501100009104
                Funded by: Lady Tata Memorial Trust 10.13039/100012117
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                dysregulated mirna,mirna biomarker,non-invasive biomarker,mirna-based therapy,oral squamous cell carcinoma

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