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microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer

BACKGROUND: The aim of this study was to identify miRNAs specifically dysregulated in BRAF-mutated colorectal cancer, which could lead to a better understanding of the molecular mechanisms underlying oncogenesis of this malignant subtype of colorectal cancer. METHODS: Candidate dysregulated miRNAs w...

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Autores principales: Takahashi, Hidekazu, Takahashi, Masanobu, Ohnuma, Shinobu, Unno, Michiaki, Yoshino, Yuki, Ouchi, Kota, Takahashi, Shin, Yamada, Yasuhide, Shimodaira, Hideki, Ishioka, Chikashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678600/
https://www.ncbi.nlm.nih.gov/pubmed/29115941
http://dx.doi.org/10.1186/s12885-017-3739-x
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author Takahashi, Hidekazu
Takahashi, Masanobu
Ohnuma, Shinobu
Unno, Michiaki
Yoshino, Yuki
Ouchi, Kota
Takahashi, Shin
Yamada, Yasuhide
Shimodaira, Hideki
Ishioka, Chikashi
author_facet Takahashi, Hidekazu
Takahashi, Masanobu
Ohnuma, Shinobu
Unno, Michiaki
Yoshino, Yuki
Ouchi, Kota
Takahashi, Shin
Yamada, Yasuhide
Shimodaira, Hideki
Ishioka, Chikashi
author_sort Takahashi, Hidekazu
collection PubMed
description BACKGROUND: The aim of this study was to identify miRNAs specifically dysregulated in BRAF-mutated colorectal cancer, which could lead to a better understanding of the molecular mechanisms underlying oncogenesis of this malignant subtype of colorectal cancer. METHODS: Candidate dysregulated miRNAs were selected in genome-wide miRNA expression array analysis using a screening set composed of 15 BRAF-mutated and 15 non-KRAS/BRAF-mutated colorectal cancers. The miRNA expressions were validated in another set of patients. The functional roles of the miRNAs were analyzed by cell growth and invasion assays. The association between miRNA expression status and the clinical outcome of patients treated with various chemotherapies was analyzed. RESULTS: Within the top five of the miRNAs screened, we validated miRNA-31 (miR-31) and miR-135b as up-regulated, while miR-193a-3p was down-regulated in BRAF-mutated cancer. Moreover, miR-193a-3p inhibited cell growth, and invasion of colorectal cancer cells. Low miR-193a-3p expression was associated with shorter progression-free survival in patients who received anti-EGFR therapy. CONCLUSIONS: Our results disclose a novel tumor suppressive role of miR-193a-3p in colorectal cancer. These results could lead to novel therapeutic strategies for colorectal cancer, particularly in BRAF-mutated colorectal cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3739-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-56786002017-11-17 microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer Takahashi, Hidekazu Takahashi, Masanobu Ohnuma, Shinobu Unno, Michiaki Yoshino, Yuki Ouchi, Kota Takahashi, Shin Yamada, Yasuhide Shimodaira, Hideki Ishioka, Chikashi BMC Cancer Research Article BACKGROUND: The aim of this study was to identify miRNAs specifically dysregulated in BRAF-mutated colorectal cancer, which could lead to a better understanding of the molecular mechanisms underlying oncogenesis of this malignant subtype of colorectal cancer. METHODS: Candidate dysregulated miRNAs were selected in genome-wide miRNA expression array analysis using a screening set composed of 15 BRAF-mutated and 15 non-KRAS/BRAF-mutated colorectal cancers. The miRNA expressions were validated in another set of patients. The functional roles of the miRNAs were analyzed by cell growth and invasion assays. The association between miRNA expression status and the clinical outcome of patients treated with various chemotherapies was analyzed. RESULTS: Within the top five of the miRNAs screened, we validated miRNA-31 (miR-31) and miR-135b as up-regulated, while miR-193a-3p was down-regulated in BRAF-mutated cancer. Moreover, miR-193a-3p inhibited cell growth, and invasion of colorectal cancer cells. Low miR-193a-3p expression was associated with shorter progression-free survival in patients who received anti-EGFR therapy. CONCLUSIONS: Our results disclose a novel tumor suppressive role of miR-193a-3p in colorectal cancer. These results could lead to novel therapeutic strategies for colorectal cancer, particularly in BRAF-mutated colorectal cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3739-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-07 /pmc/articles/PMC5678600/ /pubmed/29115941 http://dx.doi.org/10.1186/s12885-017-3739-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Article
Takahashi, Hidekazu
Takahashi, Masanobu
Ohnuma, Shinobu
Unno, Michiaki
Yoshino, Yuki
Ouchi, Kota
Takahashi, Shin
Yamada, Yasuhide
Shimodaira, Hideki
Ishioka, Chikashi
microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title_full microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title_fullStr microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title_full_unstemmed microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title_short microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer
title_sort microrna-193a-3p is specifically down-regulated and acts as a tumor suppressor in braf-mutated colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678600/
https://www.ncbi.nlm.nih.gov/pubmed/29115941
http://dx.doi.org/10.1186/s12885-017-3739-x
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