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Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway
Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduc...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172896/ https://www.ncbi.nlm.nih.gov/pubmed/25196260 http://dx.doi.org/10.1186/s12967-014-0244-8 |
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author | Xu, Lijun Zhang, Yue Wang, Hui Zhang, Guanhua Ding, Yanqing Zhao, Liang |
author_facet | Xu, Lijun Zhang, Yue Wang, Hui Zhang, Guanhua Ding, Yanqing Zhao, Liang |
author_sort | Xu, Lijun |
collection | PubMed |
description | Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduction of miR-1 suppressed cell proliferation and migration, whereas miR-1 inhibitor performed contrary functions in CRC cells. Stable overexpression of miR-1 was sufficient to inhibit tumor growth and homing capacity in vivo. Proteomic analysis revealed that miR-1 modulated the expression of key cellular molecules and involved in the MAPK and PI3K/AKT pathways by inhibiting phosphorylation of ERK and AKT. Meanwhile, miR-1 also reversed epithelial–mesenchymal transition (EMT), which played a pivotal role in the initiation of metastasis. Further studies found that miR-1 can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, identified as a CRC-associated protein. In contrast to the phenotypes induced by miR-1 restoration, LASP1-induced cell proliferation and migration partly rescued miR-1-mediated biological behaviors. Our results illustrated that miR-1 play a critical role in CRC progression, which suggests its potential role in the molecular therapy of cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0244-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4172896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41728962014-09-25 Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway Xu, Lijun Zhang, Yue Wang, Hui Zhang, Guanhua Ding, Yanqing Zhao, Liang J Transl Med Research Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduction of miR-1 suppressed cell proliferation and migration, whereas miR-1 inhibitor performed contrary functions in CRC cells. Stable overexpression of miR-1 was sufficient to inhibit tumor growth and homing capacity in vivo. Proteomic analysis revealed that miR-1 modulated the expression of key cellular molecules and involved in the MAPK and PI3K/AKT pathways by inhibiting phosphorylation of ERK and AKT. Meanwhile, miR-1 also reversed epithelial–mesenchymal transition (EMT), which played a pivotal role in the initiation of metastasis. Further studies found that miR-1 can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, identified as a CRC-associated protein. In contrast to the phenotypes induced by miR-1 restoration, LASP1-induced cell proliferation and migration partly rescued miR-1-mediated biological behaviors. Our results illustrated that miR-1 play a critical role in CRC progression, which suggests its potential role in the molecular therapy of cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0244-8) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-08 /pmc/articles/PMC4172896/ /pubmed/25196260 http://dx.doi.org/10.1186/s12967-014-0244-8 Text en © Xu et al.; licensee BioMed Central Ltd. 2014 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 work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xu, Lijun Zhang, Yue Wang, Hui Zhang, Guanhua Ding, Yanqing Zhao, Liang Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title | Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title_full | Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title_fullStr | Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title_full_unstemmed | Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title_short | Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway |
title_sort | tumor suppressor mir-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the mapk and pi3k/akt pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172896/ https://www.ncbi.nlm.nih.gov/pubmed/25196260 http://dx.doi.org/10.1186/s12967-014-0244-8 |
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