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      Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression

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          Abstract

          Background

          Breast cancer (BC) is the most commonly diagnosed cancer in women. Tumor recurrence and metastasis are the key causes of death in BC patients. Long non-coding RNA (lncRNA) is closely associated with BC progression. lncRNA nuclear-enriched abundant transcript (NEAT)1 has been reported to regulate the proliferation and mobility of several types of cancer cells. However, how lncRNA NEAT1 affects the proliferation and invasion of BC cells is not known.

          Methods

          Quantitative real time-polymerase chain reaction (qRT-PCR) was used to measure expression of lncRNA NEAT1 and microRNA (miR)-146b-5p in BC tissues and cell lines. Cell Counting Kit (CCK)-8, cell colony-formation, wound-healing, and Transwell™ assays were undertaken to determine the effects of lncRNA NEAT1 and miR-146b-5p on progression of BC cells. The interaction between lncRNA NEAT1 and miR-146b-5p was examined by luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA-pulldown assays.

          Results

          Expression of lncRNA NEAT1 was upregulated in BC tissues and cell lines. High expression of lncRNA NEAT1 predicted poor overall survival in BC patients. Silencing of expression of lncRNA NEAT1 inhibited epithelial–mesenchymal transition (EMT) and suppressed the proliferation, migration and invasion of BC cells. Ectopic expression of lncRNA NEAT1 induced EMT and promoted BC progression. Mechanistic investigations revealed that miR-146b-5p was a direct target of lncRNA NEAT1, and its expression was correlated negatively with expression of lncRNA NEAT1 in BC tissues.

          Conclusion

          lncRNA NEAT1 could (i) serve as a novel prognostic marker for BC and (ii) be a potential therapeutic target for BC.

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          Most cited references28

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          Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes.

          Triple-negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that respond differentially to chemotherapy and targeted agents. The absence of high-frequency molecular alterations and a limited number of known biomarkers have limited the development of therapeutic strategies for the disease. Herein, we summarize the results of the first round of targeted therapy approaches in TNBC and discuss new preclinical strategies. Common themes emerge from the proposed strategies, such as the use of biomarkers to identify tumours with genomic instability, targeting adapted molecular states resulting from tumour suppressor loss, and targeting altered metabolic pathways. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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            Breast Cancer: Multiple Subtypes within a Tumor?

            Breast cancer is a heterogeneous disease and stratification of tumors is paramount to achieve better clinical outcomes. While it is common to stratify and treat breast tumors as a single entity, insights from studies on intra-tumoral heterogeneity and cancer stem cells raise the possibility that multiple breast cancer subtypes may co-exist within a tumor. A role for plasticity in driving dynamic conversions between breast cancer subtypes is proposed and the clinical implications would be a need for combinatorial therapeutic strategies that account for the discrete disease entities and their plasticity. Accordingly, the advent of single-cell technologies will be crucial in enabling the diagnosis and stratification of distinct disease subtypes down to the cellular level.
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              Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

              Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                CMAR
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                21 July 2020
                2020
                : 12
                : 6091-6101
                Affiliations
                [1 ]Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital , Guangzhou, People’s Republic of China
                Author notes
                Correspondence: Songming Li Tel +86 13560013154 Email LSMGZPCH@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-0163-9685
                Article
                252295
                10.2147/CMAR.S252295
                7382757
                32801860
                e25acd23-1966-426f-be37-6ac51f9ded9b
                © 2020 Li et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 04 March 2020
                : 24 June 2020
                Page count
                Figures: 6, Tables: 1, References: 42, Pages: 11
                Categories
                Original Research

                Oncology & Radiotherapy
                lncrna neat1,mir-146b-5p,breast cancer,growth,metastasis
                Oncology & Radiotherapy
                lncrna neat1, mir-146b-5p, breast cancer, growth, metastasis

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