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...
| Publicado en: | Breast Cancer Research Vol. 21; no. 1 |
|---|---|
| Autores principales: | , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
8/7/2019
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137944826&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137944826 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 8/7/2019 vid: 21 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 137944826 137944826 NLM31391072 137944826 10.1186/s13058-019-1173-5 NLM31391072 137944826 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer. aug: au: Tan, Xiaohui Li, Zhongwu Ren, Shuchang Rezaei, Katayoon Pan, Qing Goldstein, Andrew T. Macri, Charles J. Cao, Dengfeng Brem, Rachel F. Fu, Sidney W. affil: Department of Medicine, Division of Genomic Medicine, and Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W. Ross Hall 402C, 20037, Washington, DC, USA sug: subj: Drug Resistance, Neoplasm Radiation Breast Neoplasms RNA Genes Cell Transformation, Neoplastic Breast Neoplasms Pathology Human Models, Biological Breast Neoplasms Therapy Disease Progression Female Cell Line, Tumor DNA Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Female ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|