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LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes
Long non-coding RNAs (lncRNAs) are the most heterogeneous class of non-protein-coding RNAs involved in a broad spectrum of molecular mechanisms controlling genome function, including the generation of complex networks of RNA-RNA competitive interactions. Accordingly, their dysregulation contributes...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855711/ https://www.ncbi.nlm.nih.gov/pubmed/33552987 http://dx.doi.org/10.3389/fonc.2020.614455 |
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author | Brex, Duilia Barbagallo, Cristina Mirabella, Federica Caponnetto, Angela Battaglia, Rosalia Barbagallo, Davide Caltabiano, Rosario Broggi, Giuseppe Memeo, Lorenzo Di Pietro, Cinzia Purrello, Michele Ragusa, Marco |
author_facet | Brex, Duilia Barbagallo, Cristina Mirabella, Federica Caponnetto, Angela Battaglia, Rosalia Barbagallo, Davide Caltabiano, Rosario Broggi, Giuseppe Memeo, Lorenzo Di Pietro, Cinzia Purrello, Michele Ragusa, Marco |
author_sort | Brex, Duilia |
collection | PubMed |
description | Long non-coding RNAs (lncRNAs) are the most heterogeneous class of non-protein-coding RNAs involved in a broad spectrum of molecular mechanisms controlling genome function, including the generation of complex networks of RNA-RNA competitive interactions. Accordingly, their dysregulation contributes to the onset of many tumors, including colorectal cancer (CRC). Through a combination of in silico approaches (statistical screening of expression datasets) and in vitro analyses (enforced expression, artificial inhibition, or activation of pathways), we identified LINC00483 as a potential tumor suppressor lncRNA in CRC. LINC00483 was downregulated in CRC biopsies and metastases and its decreased levels were associated with severe clinical features. Inhibition of the MAPK pathway and cell cycle arrest by starvation induced an upregulation of LINC00483, while the epithelial to mesenchymal transition activation by TGFβ-1 and IL-6 caused its down-modulation. Moreover, enforced expression of LINC00483 provoked a slowing down of cell migration rate without affecting cell proliferation. Since LINC00483 was predominantly cytoplasmic, we hypothesized a “miRNA sponge” role for it. Accordingly, we computationally reconstructed the LINC00483/miRNA/mRNA axes and evaluated the expression of mRNAs in different experimental conditions inducing LINC00483 alteration. By this approach, we identified a set of mRNAs sharing the miRNA response elements with LINC00483 and modulated in accordance with it. Moreover, we found that LINC00483 is potentially under negative control of transcription factor HNF4α. In conclusion, we propose that LINC00483 is a tumor suppressor in CRC that, through an RNA-RNA network, may control cell migration and participate in proliferation signaling. |
format | Online Article Text |
id | pubmed-7855711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78557112021-02-04 LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes Brex, Duilia Barbagallo, Cristina Mirabella, Federica Caponnetto, Angela Battaglia, Rosalia Barbagallo, Davide Caltabiano, Rosario Broggi, Giuseppe Memeo, Lorenzo Di Pietro, Cinzia Purrello, Michele Ragusa, Marco Front Oncol Oncology Long non-coding RNAs (lncRNAs) are the most heterogeneous class of non-protein-coding RNAs involved in a broad spectrum of molecular mechanisms controlling genome function, including the generation of complex networks of RNA-RNA competitive interactions. Accordingly, their dysregulation contributes to the onset of many tumors, including colorectal cancer (CRC). Through a combination of in silico approaches (statistical screening of expression datasets) and in vitro analyses (enforced expression, artificial inhibition, or activation of pathways), we identified LINC00483 as a potential tumor suppressor lncRNA in CRC. LINC00483 was downregulated in CRC biopsies and metastases and its decreased levels were associated with severe clinical features. Inhibition of the MAPK pathway and cell cycle arrest by starvation induced an upregulation of LINC00483, while the epithelial to mesenchymal transition activation by TGFβ-1 and IL-6 caused its down-modulation. Moreover, enforced expression of LINC00483 provoked a slowing down of cell migration rate without affecting cell proliferation. Since LINC00483 was predominantly cytoplasmic, we hypothesized a “miRNA sponge” role for it. Accordingly, we computationally reconstructed the LINC00483/miRNA/mRNA axes and evaluated the expression of mRNAs in different experimental conditions inducing LINC00483 alteration. By this approach, we identified a set of mRNAs sharing the miRNA response elements with LINC00483 and modulated in accordance with it. Moreover, we found that LINC00483 is potentially under negative control of transcription factor HNF4α. In conclusion, we propose that LINC00483 is a tumor suppressor in CRC that, through an RNA-RNA network, may control cell migration and participate in proliferation signaling. Frontiers Media S.A. 2021-01-20 /pmc/articles/PMC7855711/ /pubmed/33552987 http://dx.doi.org/10.3389/fonc.2020.614455 Text en Copyright © 2021 Brex, Barbagallo, Mirabella, Caponnetto, Battaglia, Barbagallo, Caltabiano, Broggi, Memeo, Di Pietro, Purrello and Ragusa http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Brex, Duilia Barbagallo, Cristina Mirabella, Federica Caponnetto, Angela Battaglia, Rosalia Barbagallo, Davide Caltabiano, Rosario Broggi, Giuseppe Memeo, Lorenzo Di Pietro, Cinzia Purrello, Michele Ragusa, Marco LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title | LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title_full | LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title_fullStr | LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title_full_unstemmed | LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title_short | LINC00483 Has a Potential Tumor-Suppressor Role in Colorectal Cancer Through Multiple Molecular Axes |
title_sort | linc00483 has a potential tumor-suppressor role in colorectal cancer through multiple molecular axes |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855711/ https://www.ncbi.nlm.nih.gov/pubmed/33552987 http://dx.doi.org/10.3389/fonc.2020.614455 |
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