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      MicroRNAs in regulation of triple-negative breast cancer progression

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          Abstract

          Purpose

          Dysregulation of miRNA profile has been associated with a broad spectrum of cellular processes underlying progression of various human malignancies. Increasing evidence suggests that specific microRNA clusters might be of clinical utility, especially in triple-negative breast carcinoma (TNBC), devoid of both predictive markers and potential therapeutic targets. Here we provide a comprehensive review of the existing data on microRNAs in TNBC, their molecular targets, a putative role in invasive progression with a particular emphasis on the epithelial-to-mesenchymal transition (EMT) and acquisition of stem-cell properties (CSC), regarded both as prerequisites for metastasis, and significance for therapy.

          Methods

          PubMed and Medline databases were systematically searched for the relevant literature. 121 articles have been selected and thoroughly analysed.

          Results

          Several miRNAs associated with EMT/CSC and invasion were identified as significantly (1) upregulated: miR-10b, miR-21, miR-29, miR-9, miR-221/222, miR-373 or (2) downregulated: miR-145, miR-199a-5p, miR-200 family, miR-203, miR-205 in TNBC. Dysregulation of miR-10b, miR-21, miR-29, miR-145, miR-200 family, miR-203, miR-221/222 was reported of prognostic value in TNBC patients.

          Conclusion

          Available data suggest that specific microRNA clusters might play an important role in biology of TNBC, understanding of which should assist disease prognostication and therapy.

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          Most cited references64

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer.

            MicroRNAs (miRNAs) are a new class of short noncoding regulatory RNAs (18-25 nucleotides) that are involved in diverse developmental and pathologic processes. Altered miRNA expression has been associated with several types of human cancer. However, most studies did not establish whether miRNA expression changes occurred within cells undergoing malignant transformation. To obtain insight into miRNA deregulation in breast cancer, we implemented an in situ hybridization (ISH) method to reveal the spatial distribution of miRNA expression in archived formalin-fixed, paraffin-embedded specimens representing normal and tumor tissue from >100 patient cases. Here, we report that expression of miR-145 and miR-205 was restricted to the myoepithelial/basal cell compartment of normal mammary ducts and lobules, whereas their accumulation was reduced or completely eliminated in matching tumor specimens. Conversely, expression of other miRNAs was detected at varying levels predominantly within luminal epithelial cells in normal tissue; expression of miR-21 was frequently increased, whereas that of let-7a was decreased in malignant cells. We also analyzed the association of miRNA expression with that of epithelial markers; prognostic indicators such as estrogen receptor, progesterone receptor, and HER2; as well as clinical outcome data. This ISH approach provides a more direct and informative assessment of how altered miRNA expression contributes to breast carcinogenesis compared with miRNA expression profiling in gross tissue biopsies. Most significantly, early manifestation of altered miR-145 expression in atypical hyperplasia and carcinoma in situ lesions suggests that this miRNA may have a potential clinical application as a novel biomarker for early detection.
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              Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1.

              We report a paracrine effect whereby endothelial cells (ECs) promote the cancer stem cell (CSC) phenotype of human colorectal cancer (CRC) cells. We showed that, without direct cell-cell contact, ECs secrete factors that promoted the CSC phenotype in CRC cells via Notch activation. In human CRC specimens, CD133 and Notch intracellular domain-positive CRC cells colocalized in perivascular regions. An EC-derived, soluble form of Jagged-1, via ADAM17 proteolytic activity, led to Notch activation in CRC cells in a paracrine manner; these effects were blocked by immunodepletion of Jagged-1 in EC-conditioned medium or blockade of ADAM17 activity. Collectively, ECs play an active role in promoting Notch signaling and the CSC phenotype by secreting soluble Jagged-1. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                +48 58 349 14 69 , rsadej@gumed.edu.pl
                +48 42 272 56 05 , hanna.romanska@gmail.com
                Journal
                J Cancer Res Clin Oncol
                J. Cancer Res. Clin. Oncol
                Journal of Cancer Research and Clinical Oncology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0171-5216
                1432-1335
                19 June 2018
                19 June 2018
                2018
                : 144
                : 8
                : 1401-1411
                Affiliations
                [1 ]ISNI 0000 0001 2165 3025, GRID grid.8267.b, Department of Pathology, , Medical University of Lodz, ; Lodz, Poland
                [2 ]ISNI 0000000113287408, GRID grid.13339.3b, Postgraduate School for Molecular Medicine, , Medical University of Warsaw, ; Warsaw, Poland
                [3 ]ISNI 0000 0001 0531 3426, GRID grid.11451.30, Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology, , University of Gdansk and Medical University of Gdansk, ; Gdansk, Poland
                Author information
                http://orcid.org/0000-0001-5360-6477
                http://orcid.org/0000-0003-3804-7042
                http://orcid.org/0000-0003-4724-3627
                http://orcid.org/0000-0003-2583-7299
                http://orcid.org/0000-0002-2328-710X
                Article
                2689
                10.1007/s00432-018-2689-2
                6061037
                29923083
                eab153a8-c04d-4772-bd4d-90d26110cae8
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 15 May 2018
                : 13 June 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004281, Narodowe Centrum Nauki;
                Award ID: UMO-2015/17/B/ NZ4/02157
                Award Recipient :
                Categories
                Review – Cancer Research
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Oncology & Radiotherapy
                triple-negative breast carcinoma,microrna,emt,csc,invasion
                Oncology & Radiotherapy
                triple-negative breast carcinoma, microrna, emt, csc, invasion

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