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      The Regulatory Role of MicroRNAs in Breast Cancer

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          Abstract

          MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.

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          Most cited references98

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          Cancer treatment and survivorship statistics, 2019

          The number of cancer survivors continues to increase in the United States because of the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate every 3 years to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries; vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics; and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Data Base are presented for the most prevalent cancer types. Cancer-related and treatment-related short-term, long-term, and late health effects are also briefly described. More than 16.9 million Americans (8.1 million males and 8.8 million females) with a history of cancer were alive on January 1, 2019; this number is projected to reach more than 22.1 million by January 1, 2030 based on the growth and aging of the population alone. The 3 most prevalent cancers in 2019 are prostate (3,650,030), colon and rectum (776,120), and melanoma of the skin (684,470) among males, and breast (3,861,520), uterine corpus (807,860), and colon and rectum (768,650) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost two-thirds (64%) are aged 65 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by follow-up care providers. Although there are growing numbers of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care.
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            RNA polymerase III transcribes human microRNAs.

            Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.
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              Revisiting the hallmarks of cancer.

              The hallmarks of cancer described by Hanahan and Weinberg have proved seminal in our understanding of cancer's common traits and in rational drug design. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 October 2019
                October 2019
                : 20
                : 19
                : 4940
                Affiliations
                [1 ]Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia; lohhuiyi.94@ 123456gmail.com (H.-Y.L.); m.afizan@ 123456upm.edu.my (N.M.A.N.A.R.); noorjahan@ 123456upm.edu.my (N.B.M.A.)
                [2 ]Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK; Brendan.Norman@ 123456liverpool.ac.uk
                [3 ]Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, UAE; laikoksong@ 123456gmail.com
                Author notes
                [* ]Correspondence: azuraidi@ 123456upm.edu.my
                Author information
                https://orcid.org/0000-0003-4835-4687
                Article
                ijms-20-04940
                10.3390/ijms20194940
                6801796
                31590453
                b7f181a3-9f26-45cc-8180-26572fb1a7f1
                © 2019 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
                : 23 July 2019
                : 23 August 2019
                Categories
                Review

                Molecular biology
                micrornas,breast cancer,oncomir,tsmir
                Molecular biology
                micrornas, breast cancer, oncomir, tsmir

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