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      Potential Regulatory Roles of MicroRNAs and Long Noncoding RNAs in Anticancer Therapies

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          Abstract

          MicroRNAs and long noncoding RNAs have long been investigated due to their roles as diagnostic and prognostic biomarkers of cancers and regulators of tumorigenesis, and the potential regulatory roles of these molecules in anticancer therapies are attracting increasing interest as more in-depth studies are performed. The major clinical therapies for cancer include chemotherapy, immunotherapy, and targeted molecular therapy. MicroRNAs and long noncoding RNAs function through various mechanisms in these approaches, and the mechanisms involve direct targeting of immune checkpoints, cooperation with exosomes in the tumor microenvironment, and alteration of drug resistance through regulation of different signaling pathways. Herein we review the regulatory functions and significance of microRNAs and long noncoding RNAs in three anticancer therapies, especially in targeted molecular therapy, and their mechanisms.

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          Cancer immunotherapy: harnessing the immune system to battle cancer.

          The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
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            Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu

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              MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2.

              A major reason for oxaliplatin chemoresistance in colorectal cancer is the acquisition of epithelial-mesenchymal transition (EMT) in cancer cells. The long noncoding RNA (lncRNA), MALAT1, is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in oxaliplatin-induced metastasis and chemoresistance is not well known. In this study, we aim to investigate the prognostic and therapeutic role of lncRNA MALAT1 in colorectal cancer patients receiving oxaliplatin-based therapy and further explore the potential transcriptional regulation through interaction with EZH2 based on the established HT29 oxaliplatin-resistant cells. Our results showed that high MALAT1 expression was associated with reduced patient survival and poor response to oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Oxaliplatin-resistant colorectal cancer cells exhibited high MALAT1 expression and EMT. LncRNA MALAT1 knockdown enhances E-cadherin expression and inhibits oxaliplatin-induced EMT in colorectal cancer cells. EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in colorectal cancer, and this association suppressed the expression of E-cadherin. Furthermore, targeted inhibition of MALAT1 or EZH2 reversed EMT and chemoresistance induced by oxaliplatin. Finally, the interaction between lncRNA MALAT1 and miR-218 was observed, which further indicated its prognostic value in patients who received standard FOLFOX (oxaliplatin combine with 5-fluorouracil and leucovorin) treatment. In conclusion, this study illuminates the prognostic role of lncRNA MALAT1 in colorectal cancer patients receiving oxaliplatin-based treatment and further demonstrates how lncRNA MALAT1 confers a chemoresistant function in colorectal cancer. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for colorectal cancer patients. Mol Cancer Ther; 16(4); 739-51. ©2017 AACR.
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                Author and article information

                Contributors
                Journal
                Mol Ther Nucleic Acids
                Mol Ther Nucleic Acids
                Molecular Therapy. Nucleic Acids
                American Society of Gene & Cell Therapy
                2162-2531
                01 September 2018
                07 December 2018
                01 September 2018
                : 13
                : 233-243
                Affiliations
                [1 ]Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
                [2 ]Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
                [3 ]Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
                Author notes
                []Corresponding author: Yongqian Shu, Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 101 Longmian Ave., Jiangning District, Nanjing 211166, China. yongqian_shu@ 123456163.com
                Article
                S2162-2531(18)30234-8
                10.1016/j.omtn.2018.08.019
                6190501
                30317163
                38d93f9e-971b-4db9-810c-42aa31317d54
                © 2018.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Article

                Molecular medicine
                micrornas,long noncoding rnas,targeted therapy,chemoresistance,immune checkpoint

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