Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer
Abstract 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 hype...
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BMC
2019-08-01
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Series: | Breast Cancer Research |
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Online Access: | http://link.springer.com/article/10.1186/s13058-019-1173-5 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaohui Tan Zhongwu Li Shuchang Ren Katayoon Rezaei Qing Pan Andrew T. Goldstein Charles J. Macri Dengfeng Cao Rachel F. Brem Sidney W. Fu |
spellingShingle |
Xiaohui Tan Zhongwu Li Shuchang Ren Katayoon Rezaei Qing Pan Andrew T. Goldstein Charles J. Macri Dengfeng Cao Rachel F. Brem Sidney W. Fu Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer Breast Cancer Research Breast cancer 21T cell lines miR-671-5p EMT Biomarkers |
author_facet |
Xiaohui Tan Zhongwu Li Shuchang Ren Katayoon Rezaei Qing Pan Andrew T. Goldstein Charles J. Macri Dengfeng Cao Rachel F. Brem Sidney W. Fu |
author_sort |
Xiaohui Tan |
title |
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_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_sort |
dynamically decreased mir-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer |
publisher |
BMC |
series |
Breast Cancer Research |
issn |
1465-542X |
publishDate |
2019-08-01 |
description |
Abstract 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. |
topic |
Breast cancer 21T cell lines miR-671-5p EMT Biomarkers |
url |
http://link.springer.com/article/10.1186/s13058-019-1173-5 |
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doaj-e6e2efed2b2e49d5ac78bd4988e682e42021-04-02T09:27:00ZengBMCBreast Cancer Research1465-542X2019-08-0121111410.1186/s13058-019-1173-5Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancerXiaohui Tan0Zhongwu Li1Shuchang Ren2Katayoon Rezaei3Qing Pan4Andrew T. Goldstein5Charles J. Macri6Dengfeng Cao7Rachel F. Brem8Sidney W. Fu9Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health SciencesDepartment of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & InstituteDepartment of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health SciencesDepartment of Pathology, The George Washington University School of Medicine and Health SciencesDepartment of Statistics, The George Washington UniversityDepartment of Obstetrics and Gynecology, The George Washington University School of Medicine and Health SciencesDepartment of Obstetrics and Gynecology, The George Washington University School of Medicine and Health SciencesDepartment of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & InstituteDepartment of Radiology, The George Washington University School of Medicine and Health SciencesDepartment of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health SciencesAbstract 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.http://link.springer.com/article/10.1186/s13058-019-1173-5Breast cancer21T cell linesmiR-671-5pEMTBiomarkers |