15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumor progression

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The contribution of lncRNAs to tumor progression and regulatory mechanisms driving their expression are areas of intense investigation. Here, we characterize the binding of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) to a nucleic acid structural element located in exon 12 of PNUTS (also known as PPP1R10) pre-RNA that regulates its alternative splicing. HnRNP E1 release from this structural element, following its silencing, nucleo-cytoplasmic translocation or in response to TGFβ, allows alternative splicing and generates a non-coding isoform of PNUTS. Functionally the lncRNA-PNUTS serves as a competitive sponge for miR-205 during epithelial-mesenchymal transition. In mesenchymal breast tumor cells and in breast tumor samples, the expression of lncRNA-PNUTS is elevated and correlates with levels of ZEB mRNAs. Thus, PNUTS is a bifunctional RNA encoding both PNUTS-mRNA and lncRNA-PNUTS each eliciting distinct biological functions. While PNUTS-mRNA is ubiquitously expressed, lncRNA-PNUTS appears to be tightly regulated dependent on hnRNP E1’s status and tumor context.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          Breast cancer metastasis: markers and models.

          Breast cancer starts as a local disease, but it can metastasize to the lymph nodes and distant organs. At primary diagnosis, prognostic markers are used to assess whether the transition to systemic disease is likely to have occurred. The prevailing model of metastasis reflects this view--it suggests that metastatic capacity is a late, acquired event in tumorigenesis. Others have proposed the idea that breast cancer is intrinsically a systemic disease. New molecular technologies, such as DNA microarrays, support the idea that metastatic capacity might be an inherent feature of breast tumours. These data have important implications for prognosis prediction and our understanding of metastasis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Alternative splicing: a pivotal step between eukaryotic transcription and translation.

            Alternative splicing was discovered simultaneously with splicing over three decades ago. Since then, an enormous body of evidence has demonstrated the prevalence of alternative splicing in multicellular eukaryotes, its key roles in determining tissue- and species-specific differentiation patterns, the multiple post- and co-transcriptional regulatory mechanisms that control it, and its causal role in hereditary disease and cancer. The emerging evidence places alternative splicing in a central position in the flow of eukaryotic genetic information, between transcription and translation, in that it can respond not only to various signalling pathways that target the splicing machinery but also to transcription factors and chromatin structure.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Origins of metastatic traits.

              How cancer cells acquire the competence to colonize distant organs remains a central question in cancer biology. Tumors can release large numbers of cancer cells into the circulation, but only a small proportion of these cells survive on infiltrating distant organs and even fewer form clinically meaningful metastases. During the past decade, many predictive gene signatures and specific mediators of metastasis have been identified, yet how cancer cells acquire these traits has remained obscure. Recent experimental work and high-resolution sequencing of human tissues have started to reveal the molecular and tumor evolutionary principles that underlie the emergence of metastatic traits. Copyright © 2013 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                100890575
                21417
                Nat Cell Biol
                Nat. Cell Biol.
                Nature cell biology
                1465-7392
                1476-4679
                23 July 2017
                21 August 2017
                September 2017
                21 February 2018
                : 19
                : 9
                : 1105-1115
                Affiliations
                [1 ]Department of Biochemistry, Medical University of South Carolina, Charleston, South Carolina 29425, USA
                [2 ]Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
                [3 ]Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA
                Author notes
                [* ]Corresponding author: Philip H. Howe, Ph.D., Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, MSC 509, Room 501, Charleston, SC 29425, Phone: 843-792-4687, Fax: 843-792-4322, howep@ 123456musc.edu
                Article
                NIHMS894389
                10.1038/ncb3595
                5578890
                28825698
                9333559f-294f-4ed7-87f2-7664c3cde4e7

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Cell biology
                serine/threonine-protein phosphatase 1 regulatory subunit 10 (ppp1r10,also known as pnuts),heterogeneous nuclear ribonucleoprotein e1 (hnrnp e1),epithelial-mesenchymal transition (emt),mir-205,alternative splicing,long noncoding rna (lncrna)

                Comments

                Comment on this article