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Published on: October 27, 2020
miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer
Xiaohui Tan1, Yebo Fu1, Liang Chen1
1Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Abstract:
MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.
Insights
MicroRNA miR-671-5p acts as a tumor suppressor in breast cancer by targeting FOXM1. Its reduced expression in invasive ductal carcinoma suggests potential as a therapeutic target for breast cancer management.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysfunction is implicated in human diseases, including cancer.
- Previous research indicated miR-671-5p dysregulation during breast cancer progression.
- This study investigates the specific role of miR-671-5p in breast tumorigenesis.
Purpose of the Study:
- To elucidate the function of miR-671-5p in breast cancer.
- To identify direct targets of miR-671-5p involved in tumorigenesis.
- To explore the therapeutic potential of miR-671-5p in breast cancer management.
Main Methods:
- Analysis of miR-671-5p expression in invasive ductal carcinoma (IDC) tissues.
- Luciferase assays to confirm direct targeting of Forkhead Box M1 (FOXM1).
- In vitro experiments involving forced expression of miR-671-5p in breast cancer cell lines, including proliferation, invasion, EMT/MET transition, cell cycle, and drug sensitivity assays.
- Host cell reactivation (HCR) assays to assess DNA repair capability.
- cDNA microarray analysis to identify differentially expressed genes.
Main Results:
- miR-671-5p expression was significantly decreased in IDC tissues compared to normal tissues.
- FOXM1 was confirmed as a direct target of miR-671-5p.
- Forced miR-671-5p expression suppressed breast cancer cell proliferation and invasion, induced S-phase arrest, and promoted a shift from EMT to MET phenotypes.
- miR-671-5p sensitized cells to chemotherapy drugs (cisplatin, 5-FU, epirubicin) and reduced DNA repair capacity.
- Gene expression profiling revealed miR-671-5p affects pathways related to cell proliferation, invasion, cell cycle, and EMT.
Conclusions:
- miR-671-5p functions as a tumor suppressor miRNA in breast cancer, primarily by targeting the oncogenic transcription factor FOXM1.
- Restoring miR-671-5p levels inhibits tumor growth, metastasis, and enhances chemosensitivity.
- miR-671-5p represents a promising novel therapeutic target for breast cancer treatment.
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