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      The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition

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          Abstract

          Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets.

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          Most cited references194

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Regulatory networks defining EMT during cancer initiation and progression.

            Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.
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              The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

              Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                26 March 2021
                2021
                : 8
                : 665199
                Affiliations
                [1] 1Pharmacognosy Department, College of Pharmacy, Hawler Medical University , Erbil, Iraq
                [2] 2Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences , Birjand, Iran
                [3] 3Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University , Winston-Salem, NC, United States
                [4] 4School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, NSW, Australia
                [5] 5Department of Biology, College of Education, Salahaddin University-Erbil , Erbil, Iraq
                [6] 6Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [7] 7Department of Medical Genetics, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                Author notes

                Edited by: Yu Xiao, Wuhan University, China

                Reviewed by: Ali Zarrabi, Sabanc ı University, Turkey; Tian Hong, The University of Tennessee, Knoxville, United States

                *Correspondence: Mohammad Taheri, mohammad_823@ 123456yahoo.com
                Soudeh Ghafouri-Fard, S.ghafourifard@ 123456sbmu.ac.ir

                This article was submitted to Protein and RNA Networks, a section of the journal Frontiers in Molecular Biosciences

                Article
                10.3389/fmolb.2021.665199
                8033041
                33842553
                545f1254-511c-4914-9d0f-c5a9d01c2c91
                Copyright © 2021 Hussen, Shoorei, Mohaqiq, Dinger, Hidayat, Taheri and Ghafouri-Fard.

                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
                : 07 February 2021
                : 01 March 2021
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 194, Pages: 12, Words: 0
                Categories
                Molecular Biosciences
                Review

                lncrna,mirna,epithelial to mesenchymal transition,expression,biomarker

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