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      MicroRNAs Modulate Drug Resistance-Related Mechanisms in Hepatocellular Carcinoma

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          Abstract

          Primary liver cancer [hepatocellular carcinoma (HCC)] is one of the most common malignant tumors worldwide, causing serious health threats because of its high morbidity and mortality, rapid growth, and strong invasiveness. Patients with HCC frequently develop resistance to the current chemotherapeutic drugs, and this is largely attributed to the high-level heterogeneity of the tumor tissue. MicroRNAs (miRNAs) are a group of master regulators for multiple physiological and pathological processes and play important roles in the tumorigenesis. More recent studies have indicated that miRNAs also play a non-negligible role in the development of drug resistance in liver cancer. In this review, we summarize the data from the latest studies on the mechanisms of drug resistance in liver cancer, including autophagy, membrane transporters, epithelial–mesenchymal transitions (EMTs), tumor microenvironment, and genes and proteins that are associated with apoptosis. The data herein will provide valuable information for the development of novel approaches to tackle drug resistance in the management of liver cancer.

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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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            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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              Autophagy and multidrug resistance in cancer

              Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
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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
                30 June 2020
                2020
                : 10
                : 920
                Affiliations
                [1] 1Department of Health Toxicology, Xiangya School of Public Health, Central South University , Changsha, China
                [2] 2Department of Radiology, The Third Xiangya Hospital, Central South University , Changsha, China
                [3] 3Storr Liver Center, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital , Westmead, NSW, Australia
                Author notes

                Edited by: Xiaofang Xing, Peking University Cancer Hospital, China

                Reviewed by: Regine Schneider-Stock, University of Erlangen Nuremberg, Germany; Lin Wang, New York University, United States

                *Correspondence: Liang Qiao liang.qiao@ 123456sydney.edu.au

                This article was submitted to Gastrointestinal Cancers, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work

                Article
                10.3389/fonc.2020.00920
                7338562
                32695666
                0e42ab77-734d-4fd8-8e27-c474e035fe88
                Copyright © 2020 Liang, Liang, Qiao and Xiao.

                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
                : 02 February 2020
                : 11 May 2020
                Page count
                Figures: 5, Tables: 4, Equations: 0, References: 127, Pages: 13, Words: 9792
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                micrornas,drug resistance,hepatocellular carcinoma,autophagy,tumor microenvironment

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