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      Is Open Access

      Long Non-coding RNAs Involved in Resistance to Chemotherapy in Ovarian Cancer

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          Abstract

          Ovarian cancer (OC) accounts for more than 150,000 deaths worldwide every year. Patients are often diagnosed at an advanced stage with metastatic dissemination. Although platinum- and taxane-based chemotherapies are effective treatment options, they are rarely curative and eventually, the disease will progress due to acquired resistance. Emerging evidence suggests a crucial role of long non-coding RNAs (lncRNAs) in the response to therapy in OC. Transcriptome profiling studies using high throughput approaches have identified differential expression patterns of lncRNAs associated with disease recurrence. Furthermore, several aberrantly expressed lncRNAs in resistant OC cells have been related to increased cell division, improved DNA repair, up-regulation of drug transporters or reduced susceptibility to apoptotic stimuli, supporting their involvement in acquired resistance. In this review, we will discuss the key aspects of lncRNAs associated with the development of resistance to platinum- and taxane-based chemotherapy in OC. The molecular landscape of OC will be introduced, to provide a background for understanding the role of lncRNAs in the acquisition of malignant properties. We will focus on the interplay between lncRNAs and molecular pathways affecting drug response to evaluate their impact on treatment resistance. Additionally, we will discuss the prospects of using lncRNAs as biomarkers or targets for precision medicine in OC. Although there is still plenty to learn about lncRNAs and technical challenges to be solved, the evidence of their involvement in OC and the development of acquired resistance are compelling and warrant further investigation for clinical applications.

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          Most cited references126

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          Ovarian cancer

          Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors offer potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r

            The H19 large intergenic noncoding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extraembryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded within H19’s first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extraembryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth promoting Insulin-like growth factor 1 receptor (Igf1r). Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress response RNA binding protein HuR. These results suggest that H19’s main physiological role is in limiting growth of the placenta prior to birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.
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              Platinum Compounds: a New Class of Potent Antitumour Agents

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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
                21 January 2020
                2019
                : 9
                : 1549
                Affiliations
                [1] 1Department of Clinical Genetics, Lillebaelt Hospital-University Hospital of Southern Denmark , Vejle, Denmark
                [2] 2Department of Clinical Oncology, Lillebaelt Hospital-University Hospital of Southern Denmark , Vejle, Denmark
                [3] 3Institute of Regional Health Research, University of Southern Denmark , Odense, Denmark
                Author notes

                Edited by: Deilson Elgui De Oliveira, São Paulo State University, Brazil

                Reviewed by: Monica Montopoli, University of Padova, Italy; Raphael Carmo Valente, Rio de Janeiro State University, Brazil

                *Correspondence: Silvia R. Rogatto silvia.regina.rogatto@ 123456rsyd.dk

                This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2019.01549
                6985280
                32039022
                bcc21844-d789-40bb-b97a-b6816ef23e89
                Copyright © 2020 Abildgaard, Do Canto, Steffensen and Rogatto.

                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
                : 09 August 2019
                : 20 December 2019
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 196, Pages: 17, Words: 13434
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                ovarian cancer,lncrna,drug resistance,chemotherapy,precision medicine
                Oncology & Radiotherapy
                ovarian cancer, lncrna, drug resistance, chemotherapy, precision medicine

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