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      MicroRNAs and Long Non-Coding RNAs and Their Hormone-Like Activities in Cancer

      review-article
      1 , 2 , 3 , * , 1 , 4 , 5 , *
      Cancers
      MDPI
      non-coding RNAs, microRNAs, long non-coding RNAs, hormones, hormone-like action

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          Abstract

          Hormones are messengers circulating in the body that interact with specific receptors on the cell membrane or inside the cells and regulate, at a distal site, the activities of specific target organs. The definition of hormone has evolved in the last years. Hormones are considered in the context of cell–cell communication and mechanisms of cellular signaling. The best-known mechanisms of this kind are chemical receptor-mediated events, the cell–cell direct interactions through synapses, and, more recently, the extracellular vesicle (EV) transfer between cells. Recently, it has been extensively demonstrated that EVs are used as a way of communication between cells and that they are transporters of specific messenger signals including non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Circulating ncRNAs in body fluids and extracellular fluid compartments may have endocrine hormone-like effects because they can act at a distance from secreting cells with widespread consequences within the recipient cells. Here, we discuss and report examples of the potential role of miRNAs and lncRNAs as mediator for intercellular communication with a hormone-like mechanism in cancer.

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          Most cited references44

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          Regulation of microRNA function in animals

          Since their serendipitous discovery in nematodes, microRNAs (miRNAs) have emerged as key regulators of biological processes in animals. These small RNAs form complex regulatory networks in cell development, differentiation and homeostasis. Deregulation of miRNA function is associated with an increasing number of human diseases, particularly cancer. Recent discoveries have expanded our understanding of how miRNAs are regulated. Here we review the mechanisms that modulate miRNA activity, their stability and their localization through alternative processing, sequence editing, post-translational modifications of Argonaute proteins, viral factors, transport from the cytoplasm and regulation of miRNA–target interactions. We conclude by discussing intriguing open questions to be answered by future research.
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            MicroRNA control of signal transduction.

            MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
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              GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.

              Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                17 March 2019
                March 2019
                : 11
                : 3
                : 378
                Affiliations
                [1 ]Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Boulevard, Unit 422, Houston, TX 77030, USA
                [2 ]Department of Medical Sciences, University of Turin, Turin 10126, Italy
                [3 ]Italian Institute for Genomic Medicine (IIGM), Turin 10126, Italy
                [4 ]Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                [5 ]Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                Author notes
                [* ]Correspondence: BPardini@ 123456mdanderson.org (B.P.); gcalin@ 123456mdanderson.org (G.A.C.); Tel.: +1-713-792-5461 (G.A.C.)
                Article
                cancers-11-00378
                10.3390/cancers11030378
                6468345
                30884898
                9acfdeed-7708-4538-8c26-903b5c8fcf0f
                © 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
                : 31 January 2019
                : 11 March 2019
                Categories
                Review

                non-coding rnas,micrornas,long non-coding rnas,hormones,hormone-like action

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