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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...

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Autores principales: Xu, Qi, Tong, Jin-Lu, Zhang, Chen-Peng, Xiao, Qian, Lin, Xiao-Lin, Xiao, Xiu-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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.
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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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