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Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells
The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568930/ https://www.ncbi.nlm.nih.gov/pubmed/26082201 http://dx.doi.org/10.1111/jcmm.12617 |
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author | Alfano, Daniela Gorrasi, Anna Li Santi, Anna Ricci, Patrizia Montuori, Nunzia Selleri, Carmine Ragno, Pia |
author_facet | Alfano, Daniela Gorrasi, Anna Li Santi, Anna Ricci, Patrizia Montuori, Nunzia Selleri, Carmine Ragno, Pia |
author_sort | Alfano, Daniela |
collection | PubMed |
description | The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. |
format | Online Article Text |
id | pubmed-4568930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45689302015-09-17 Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells Alfano, Daniela Gorrasi, Anna Li Santi, Anna Ricci, Patrizia Montuori, Nunzia Selleri, Carmine Ragno, Pia J Cell Mol Med Original Articles The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. John Wiley & Sons, Ltd 2015-09 2015-06-16 /pmc/articles/PMC4568930/ /pubmed/26082201 http://dx.doi.org/10.1111/jcmm.12617 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Alfano, Daniela Gorrasi, Anna Li Santi, Anna Ricci, Patrizia Montuori, Nunzia Selleri, Carmine Ragno, Pia Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title | Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title_full | Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title_fullStr | Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title_full_unstemmed | Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title_short | Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells |
title_sort | urokinase receptor and cxcr4 are regulated by common micrornas in leukaemia cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568930/ https://www.ncbi.nlm.nih.gov/pubmed/26082201 http://dx.doi.org/10.1111/jcmm.12617 |
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