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      Autophagy-Regulating microRNAs and Cancer

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          Abstract

          Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway that is responsible for the degradation of long-lived proteins, protein aggregates, as well as damaged organelles in order to maintain cellular homeostasis. Consequently, abnormalities of autophagy are associated with a number of diseases, including Alzheimers’s disease, Parkinson’s disease, and cancer. According to the current view, autophagy seems to serve as a tumor suppressor in the early phases of cancer formation, yet in later phases, autophagy may support and/or facilitate tumor growth, spread, and contribute to treatment resistance. Therefore, autophagy is considered as a stage-dependent dual player in cancer. microRNAs (miRNAs) are endogenous non-coding small RNAs that negatively regulate gene expression at a post-transcriptional level. miRNAs control several fundamental biological processes, and autophagy is no exception. Furthermore, accumulating data in the literature indicate that dysregulation of miRNA expression contribute to the mechanisms of cancer formation, invasion, metastasis, and affect responses to chemotherapy or radiotherapy. Therefore, considering the importance of autophagy for cancer biology, study of autophagy-regulating miRNA in cancer will allow a better understanding of malignancies and lead to the development of novel disease markers and therapeutic strategies. The potential to provide study of some of these cancer-related miRNAs were also implicated in autophagy regulation. In this review, we will focus on autophagy, miRNA, and cancer connection, and discuss its implications for cancer biology and cancer treatment.

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          Most cited references190

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          The role of Atg proteins in autophagosome formation.

          Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.
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            MicroRNA biogenesis: coordinated cropping and dicing.

            V Kim (2005)
            The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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              Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.

              The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice suffer from a high incidence of spontaneous tumors. These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1-/- embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.
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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
                18 April 2017
                2017
                : 7
                : 65
                Affiliations
                [1] 1Molecular Biology, Genetics and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University , Istanbul, Turkey
                [2] 2Center of Excellence for Functional Surfaces and Interfaces for Nano Diagnostics (EFSUN), Sabanci University , Istanbul, Turkey
                Author notes

                Edited by: Patrizia Agostinis, State University of Leuven, Belgium

                Reviewed by: Giovanni Blandino, Istituti Fisioterapici Ospitalieri (IRCCS), Italy; Stefano Fais, Istituto Superiore di Sanità, Italy; Francesco Di Raimondo, University of Catania, Italy

                *Correspondence: Devrim Gozuacik, dgozuacik@ 123456sabanciuniv.edu

                These authors have contributed equally to this work as second authors.

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

                Article
                10.3389/fonc.2017.00065
                5394422
                28459042
                550f4351-8a95-41e9-be7e-43a7f0863af4
                Copyright © 2017 Gozuacik, Akkoc, Ozturk and Kocak.

                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) or licensor 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
                : 30 December 2016
                : 21 March 2017
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 259, Pages: 22, Words: 19944
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                autophagy,microrna,post-transcriptional control,cancer growth,metastasis,chemotherapy,radiotherapy,biomarker

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