69
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

      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

          MicroRNA-155 (miR-155) is frequently up-regulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau tumour suppressor (VHL) in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited HUVEC network formation, proliferation, invasion, and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis, and recruitment of pro-inflammatory cells such as tumour associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late stage, lymph node metastasis, and poor prognosis as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 plays a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore, miR-155 is an important therapeutic target in breast cancer.

          Related collections

          Most cited references25

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

          Angiogenesis in cancer, vascular, rheumatoid and other disease.

          J Folkman (1995)
          Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Molecular regulation of vessel maturation.

            The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature--a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Accumulation of miR-155 and BIC RNA in human B cell lymphomas.

              We show that the microRNA miR-155 can be processed from sequences present in BIC RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in lymphoma cells. The precursor of miR-155 is likely a transient spliced or unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is primarily cytoplasmic. By using a sensitive and quantitative assay, we find that clinical isolates of several types of B cell lymphomas, including diffuse large B cell lymphoma (DLBCL), have 10- to 30-fold higher copy numbers of miR-155 than do normal circulating B cells. Similarly, the quantities of BIC RNA are elevated in lymphoma cells, but ratios of the amounts of the two RNAs are not constant, suggesting that the level of miR-155 is controlled by transcription and processing. Significantly higher levels of miR-155 are present in DLBCLs with an activated B cell phenotype than with the germinal center phenotype. Because patients with activated B cell-type DLBCL have a poorer clinical prognosis, quantification of this microRNA may be diagnostically useful.
                Bookmark

                Author and article information

                Journal
                8711562
                6325
                Oncogene
                Oncogene
                Oncogene
                0950-9232
                1476-5594
                4 February 2014
                28 January 2013
                6 February 2014
                06 August 2014
                : 33
                : 6
                : 679-689
                Affiliations
                [1 ]Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
                [2 ]Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
                [3 ]Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
                [4 ]Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
                [5 ]Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
                Author notes
                Correspondence to: JQ Cheng, PhD, MD, Departments of Molecular Oncology, H. Lee Moffitt cancer Center and Research Institute, 12909 Magnolia Dr., SRB3, Tampa, FL 33612. Jin.Cheng@ 123456moffitt.org
                [*]

                Authors contributed equally to this work.

                Article
                NIHMS490232
                10.1038/onc.2012.636
                3925335
                23353819
                8b832294-403e-4e5a-b503-fa5f3df3966d

                Users may view, print, copy, download and 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
                Funding
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA160455 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA137041 || CA
                Categories
                Article

                Oncology & Radiotherapy
                mir-155,angiogenesis,vhl,breast cancer,inflammation
                Oncology & Radiotherapy
                mir-155, angiogenesis, vhl, breast cancer, inflammation

                Comments

                Comment on this article