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      miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

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          Abstract

          MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR‐495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR‐495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol‐doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre‐treatment with miR‐495 before chemotherapy could improve the curative effect on MDR1‐based MDR cancer.

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          Most cited references38

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          Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites

          mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.
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            Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches.

            Multi-drug resistance (MDR) has become the largest obstacle to the success of cancer chemotherapies. The mechanisms of MDR and the approaches to test MDR have been discovered, yet not fully understood. This review covers the in vivo and in vitro approaches for the detection of MDR in the laboratory and the mechanisms of MDR in cancers. This study also envisages the future developments toward the clinical and therapeutic applications of MDR in cancer treatment. Future therapeutics for cancer treatment will likely combine the existing therapies with drugs originated from MDR mechanisms such as anti-cancer stem cell drugs, anti-miRNA drugs or anti-epigenetic drugs. The challenges for the clinical detection of MDR will be to find new biomarkers and to determine new evaluation systems before the drug resistance emerges. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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              Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin.

              Many chemotherapy regiments are successfully used to treat breast cancer; however, often breast cancer cells develop drug resistance that usually leads to a relapse and worsening of prognosis. We have shown recently that epigenetic changes such as DNA methylation and histone modifications play an important role in breast cancer cell resistance to chemotherapeutic agents. Another mechanism of gene expression control is mediated via the function of small regulatory RNA, particularly microRNA (miRNA); its role in cancer cell drug resistance still remains unexplored. In the present study, we investigated the role of miRNA in the resistance of human MCF-7 breast adenocarcinoma cells to doxorubicin (DOX). Here, we for the first time show that DOX-resistant MCF-7 cells (MCF-7/DOX) exhibit a considerable dysregulation of the miRNAome profile and altered expression of miRNA processing enzymes Dicer and Argonaute 2. The mechanistic link of miRNAome deregulation and the multidrug-resistant phenotype of MCF-7/DOX cells was evidenced by a remarkable correlation between specific miRNA expression and corresponding changes in protein levels of their targets, specifically those ones that have a documented role in cancer drug resistance. Furthermore, we show that microRNA-451 regulates the expression of multidrug resistance 1 gene. More importantly, transfection of the MCF-7/DOX-resistant cells with microRNA-451 resulted in the increased sensitivity of cells to DOX, indicating that correction of altered expression of miRNA may have significant implications for therapeutic strategies aiming to overcome cancer cell resistance.
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                Author and article information

                Contributors
                sokuren@163.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                14 April 2017
                September 2017
                : 21
                : 9 ( doiID: 10.1111/jcmm.2017.21.issue-9 )
                : 1929-1943
                Affiliations
                [ 1 ] Tumor Institute Taizhou University Taizhou ZJ China
                [ 2 ] Biochemistry Department of Purdue University West Lafayette IN USA
                [ 3 ] Chemistry Department of Shangrao Normal University Shangrao JX China
                [ 4 ] Life science College of Nanjing Agricultural University Nanjing JS China
                [ 5 ] Radiology Department of Taizhou Hospital Taizhou ZJ China
                Author notes
                [*] [* ] Correspondence to: Zhenyou ZOU

                E‐mail: sokuren@ 123456163.com

                Article
                JCMM13114
                10.1111/jcmm.13114
                5571520
                28411377
                fadef49d-ab1f-4f5b-a8fd-2e67dfb43598
                © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 August 2016
                : 04 January 2017
                Page count
                Figures: 8, Tables: 0, Pages: 15, Words: 9341
                Funding
                Funded by: Zhejiang Provincial Nature and Science Fund
                Award ID: Y17H160027
                Funded by: Public Welfare Technology Research Grant for Zhejiang Social Development
                Award ID: 2015C33248
                Funded by: Taizhou University Research Fund
                Award ID: 0104010004
                Funded by: Taizhou University Talent Fostering Fund
                Award ID: 2015PY028
                Funded by: Tumor Institute of Taizhou University
                Award ID: 2012R428024
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                jcmm13114
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.8 mode:remove_FC converted:25.08.2017

                Molecular medicine
                mir‐495,multidrug resistance,multidrug resistance protein 1
                Molecular medicine
                mir‐495, multidrug resistance, multidrug resistance protein 1

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