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miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4
AIM: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains uncle...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655427/ https://www.ncbi.nlm.nih.gov/pubmed/29065177 http://dx.doi.org/10.1371/journal.pone.0186718 |
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author | Xu, Qi Tong, Jin-Lu Zhang, Chen-Peng Xiao, Qian Lin, Xiao-Lin Xiao, Xiu-Ying |
author_facet | Xu, Qi Tong, Jin-Lu Zhang, Chen-Peng Xiao, Qian Lin, Xiao-Lin Xiao, Xiu-Ying |
author_sort | Xu, Qi |
collection | PubMed |
description | AIM: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. METHODS: miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. RESULTS: We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. CONCLUSIONS: Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. |
format | Online Article Text |
id | pubmed-5655427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56554272017-11-09 miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 Xu, Qi Tong, Jin-Lu Zhang, Chen-Peng Xiao, Qian Lin, Xiao-Lin Xiao, Xiu-Ying PLoS One Research Article AIM: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. METHODS: miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. RESULTS: We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. CONCLUSIONS: Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. Public Library of Science 2017-10-24 /pmc/articles/PMC5655427/ /pubmed/29065177 http://dx.doi.org/10.1371/journal.pone.0186718 Text en © 2017 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Xu, Qi Tong, Jin-Lu Zhang, Chen-Peng Xiao, Qian Lin, Xiao-Lin Xiao, Xiu-Ying miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title | miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title_full | miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title_fullStr | miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title_full_unstemmed | miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title_short | miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4 |
title_sort | mir-27a induced by colon cancer cells in hlecs promotes lymphangiogenesis by targeting smad4 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655427/ https://www.ncbi.nlm.nih.gov/pubmed/29065177 http://dx.doi.org/10.1371/journal.pone.0186718 |
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