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Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer
BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686561/ https://www.ncbi.nlm.nih.gov/pubmed/31391072 http://dx.doi.org/10.1186/s13058-019-1173-5 |
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author | Tan, Xiaohui Li, Zhongwu Ren, Shuchang Rezaei, Katayoon Pan, Qing Goldstein, Andrew T. Macri, Charles J. Cao, Dengfeng Brem, Rachel F. Fu, Sidney W. |
author_facet | Tan, Xiaohui Li, Zhongwu Ren, Shuchang Rezaei, Katayoon Pan, Qing Goldstein, Andrew T. Macri, Charles J. Cao, Dengfeng Brem, Rachel F. Fu, Sidney W. |
author_sort | Tan, Xiaohui |
collection | PubMed |
description | BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment. METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed. RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability. CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-019-1173-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6686561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66865612019-08-12 Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer Tan, Xiaohui Li, Zhongwu Ren, Shuchang Rezaei, Katayoon Pan, Qing Goldstein, Andrew T. Macri, Charles J. Cao, Dengfeng Brem, Rachel F. Fu, Sidney W. Breast Cancer Res Research Article BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment. METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed. RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability. CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-019-1173-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-07 2019 /pmc/articles/PMC6686561/ /pubmed/31391072 http://dx.doi.org/10.1186/s13058-019-1173-5 Text en © The Author(s). 2019 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 Tan, Xiaohui Li, Zhongwu Ren, Shuchang Rezaei, Katayoon Pan, Qing Goldstein, Andrew T. Macri, Charles J. Cao, Dengfeng Brem, Rachel F. Fu, Sidney W. Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title | Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title_full | Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title_fullStr | Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title_full_unstemmed | Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title_short | Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
title_sort | dynamically decreased mir-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686561/ https://www.ncbi.nlm.nih.gov/pubmed/31391072 http://dx.doi.org/10.1186/s13058-019-1173-5 |
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