miR-200c-3p regulates α4 integrin-mediated T cell adhesion and migration.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2422 (Electronic) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando Fl : Academic Press
      Original Publication: New York, Academic Press.
    • Subject Terms:
      MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Integrin alpha4*/metabolism ; Integrin alpha4*/genetics ; Cell Movement*/genetics ; Cell Adhesion*/genetics ; T-Lymphocytes*/metabolism; Humans ; Proto-Oncogene Protein c-ets-1/metabolism ; Proto-Oncogene Protein c-ets-1/genetics ; Mucoproteins/genetics ; Mucoproteins/metabolism ; Transforming Growth Factor beta1/metabolism ; Immunoglobulins/genetics ; Immunoglobulins/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Adhesion Molecules/genetics ; Cell Line
    • Abstract:
      A microRNA miR-200c-3p is a regulator of epithelial-mesenchymal transition to control adhesion and migration of epithelial and mesenchymal cells. However, little is known about whether miR-200c-3p affects lymphocyte adhesion and migration mediated by integrins. Using TK-1 (a T lymphoblast cell) as a model of T cell, here we show that repressed expression of miR-200c-3p upregulated α4 integrin-mediated adhesion to and migration across mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Conversely, overexpression of miR-200c-3p downregulated α4 integrin-mediated adhesion and migration. Unlike in epithelial cells, miR-200c-3p did not target talin, a conformation activator of integrin, but, targeted E26-transformation-specific sequence 1 (ETS1), a transcriptional activator of α4 integrin, in T cells. Treatment of the miR-200c-3p-low-expressing TK-1 cells that possessed elevated α4 integrin with ETS1 small interfering RNA (siRNA) resulted in the reversion of the α4 integrin expression, supporting that ETS1 is a target of miR-200c-3p. A potential proinflammatory immune-modulator retinoic acid (RA) treatment of TK-1 cells elicited a significant reduction of miR-200c-3p and simultaneously a marked increase in ETS1 and α4 integrin expression. An anti-inflammatory cytokine TGF-β1 treatment elevated miR-200c-3p, thereby downregulating ETS1 and α4 integrin expression. These results suggest that miR-200c-3p is an important regulator of α4 integrin expression and functions and may be controlled by RA and TGF-β1 in an opposite way. Overexpression of miR-200c-3p could be a novel therapeutic option for treatment of gut inflammation through suppressing α4 integrin-mediated T cell migration.
      Competing Interests: Declaration of competing interest None.
      (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: ETS1; MAdCAM-1; T cell; miR-200c-3p; α4 integrin
    • Accession Number:
      0 (MicroRNAs)
      143198-26-9 (Integrin alpha4)
      0 (MIRN200 microRNA, human)
      0 (Proto-Oncogene Protein c-ets-1)
      0 (ETS1 protein, human)
      0 (Mucoproteins)
      0 (Transforming Growth Factor beta1)
      0 (Immunoglobulins)
      0 (MADCAM1 protein, human)
      0 (Cell Adhesion Molecules)
    • Publication Date:
      Date Created: 20240627 Date Completed: 20240714 Latest Revision: 20240812
    • Publication Date:
      20240813
    • Accession Number:
      10.1016/j.yexcr.2024.114146
    • Accession Number:
      38936759