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      Role of microRNAs as Clinical Cancer Biomarkers for Ovarian Cancer: A Short Overview

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          Abstract

          Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs are promising biomarkers in this respect. In this paper, we review the most recent advances regarding the alterations of microRNAs in ovarian cancer. We have briefly described the contribution of miRNAs in the mechanisms of ovarian cancer invasion, metastasis, and chemotherapy sensitivity. We have also summarized the alterations underwent by microRNAs in solid ovarian tumors, in animal models for ovarian cancer, and in various ovarian cancer cell lines as compared to previous reviews that were only focused the circulating microRNAs as biomarkers. In this context, we consider that the biomarker screening should not be limited to circulating microRNAs per se, but rather to the simultaneous detection of the same microRNA alteration in solid tumors, in order to understand the differences between the detection of nucleic acids in early vs. late stages of cancer. Moreover, in vitro and in vivo models should also validate these microRNAs, which could be very helpful as preclinical testing platforms for pharmacological and/or molecular genetic approaches targeting microRNAs. The enormous quantity of data produced by preclinical and clinical studies regarding the role of microRNAs that act synergistically in tumorigenesis mechanisms that are associated with ovarian cancer subtypes, should be gathered, integrated, and compared by adequate methods, including molecular clustering. In this respect, molecular clustering analysis should contribute to the discovery of best biomarkers-based microRNAs assays that will enable rapid, efficient, and cost-effective detection of ovarian cancer in early stages. In conclusion, identifying the appropriate microRNAs as clinical biomarkers in ovarian cancer might improve the life quality of patients.

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          Targeting microRNAs in cancer: rationale, strategies and challenges.

          MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that regulate gene expression. Early studies have shown that miRNA expression is deregulated in cancer and experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression. Based on these observations, miRNA-based anticancer therapies are being developed, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. The advantage of using miRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. In this Review, we describe the role of miRNAs in tumorigenesis and critically discuss the rationale, the strategies and the challenges for the therapeutic targeting of miRNAs in cancer.
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            miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response.

            Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials.
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              High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints

              Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                09 January 2020
                January 2020
                : 9
                : 1
                : 169
                Affiliations
                [1 ]Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independenței, 050095 Bucharest, Romania; elena.necsulescu@ 123456drd.unibuc.ro (C.E.S.); calin.rusu@ 123456nipne.ro (C.M.R.); beatrice.radu@ 123456bio.unibuc.ro (B.M.R.)
                [2 ]Center for Advanced Laser Technologies (CETAL), National Institute for Laser, Plasma and Radiation Physics, 409 Atomiștilor St., 77125 Măgurele, Romania
                [3 ]Department of General Surgery, Sf. Maria Clinical Hospital, ‘Carol Davila’ University of Medicine and Pharmacy, 37–39 Ion Mihalache Blvd., 011172 Bucharest, Romania; drpredescu@ 123456yahoo.com
                [4 ]Department of Life and Environmental Sciences, ‘Horia Hulubei’ National Institute of Physics and Nuclear Engineering, 30 Reactorului, 077125 Măgurele, Romania
                [5 ]Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest (ICUB), University of Bucharest, 91–95 Splaiul Independenţei, 050095 Bucharest, Romania
                [6 ]Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania; dragos@ 123456cretoiu.ro
                [7 ]Fetal Medicine Excellence Research Center, ‘Alessandrescu-Rusescu’ National Institute of Mother and Child Health, 120 Lacul Tei Blvd., 020395 Bucharest, Romania; nsuciu54@ 123456yahoo.com
                [8 ]Department of Surgical Oncology, Alexandru Trestioreanu Oncology Institute, ‘Carol Davila’ University of Medicine and Pharmacy, 252 Fundeni Rd., 022328 Bucharest, Romania; dr.voineasilviu@ 123456gmail.com
                Author notes
                [* ]Correspondence: sanda@ 123456cretoiu.ro
                [†]

                Authors have contributed equally.

                Author information
                https://orcid.org/0000-0003-4421-2163
                https://orcid.org/0000-0003-3214-030X
                https://orcid.org/0000-0003-2575-4880
                Article
                cells-09-00169
                10.3390/cells9010169
                7016727
                31936634
                656a4231-888c-4c1e-a380-b10a99c32b40
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 November 2019
                : 06 January 2020
                Categories
                Review

                ovarian cancer,microrna,biomarker,early diagnosis,molecular clustering analysis

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