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      Piwi-interacting RNAs in cancer: emerging functions and clinical utility

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          Abstract

          PIWI-interacting RNAs (piRNAs) are emerging players in cancer genomics. Originally described in the germline, there are over 20,000 piRNA genes in the human genome. In contrast to microRNAs, piRNAs interact with PIWI proteins, another member of the Argonaute family, and function primarily in the nucleus. There, they are involved in the epigenetic silencing of transposable elements in addition to the transcriptional regulation of genes. It has recently been demonstrated that piRNAs are also expressed across a variety of human somatic tissue types in a tissue-specific manner. An increasing number of studies have shown that aberrant piRNA expression is a signature feature across multiple tumour types; however, their specific tumorigenic functions remain unclear. In this article, we discuss the emerging functional roles of piRNAs in a variety of cancers, and highlight their potential clinical utilities.

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          Most cited references64

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          Small silencing RNAs: an expanding universe.

          Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.
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            Mobile elements: drivers of genome evolution.

            Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.
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              A germline-specific class of small RNAs binds mammalian Piwi proteins.

              Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.
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                Author and article information

                Contributors
                kng@bccrc.ca
                canderson@bccrc.ca
                emarshall@bccrc.ca
                bminatel@bccrc.ca
                kenfield@bccrc.ca
                hlsaprunoff@bccrc.ca
                wanlam@bccrc.ca
                vmartinez@bccrc.ca
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                15 January 2016
                15 January 2016
                2016
                : 15
                : 5
                Affiliations
                Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada
                Article
                491
                10.1186/s12943-016-0491-9
                4714483
                26768585
                67e1a738-9904-468f-9d49-f8ef07c457f7
                © Ng et al. 2016

                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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 August 2015
                : 5 January 2016
                Funding
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000147, Canadian Breast Cancer Foundation (CA);
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100005614, BC Cancer Agency (CA);
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research (CA);
                Funded by: FundRef http://dx.doi.org/10.13039/501100000066, Canadian Child Health Clinician Scientist Program (CA);
                Award ID: FDN-143345
                Award Recipient :
                Funded by: APESP (São Paulo Research Foundation)
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                piwi-interacting rna,pirna,piwi,cancer,tissue specificity,transcriptome,small rna,non-coding rna,epigenetics

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