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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-149 Inhibits Non-Small-Cell Lung Cancer Cells EMT by Targeting FOXM1
Yang Ke1, Weiyong Zhao, Jie Xiong
1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
MicroRNAs (miRNAs) have been implied to play crucial roles for epithelial-to-mesenchymal transition (EMT) of non-small-cell lung cancer cells (NSCLC cells). Here we found that the expression of miR-149, downregulated in lung cancer, was inversely correlated with invasive capability and the EMT phenotype of NSCLC cells. miR-149 inhibited EMT in NSCLC cells. Furthermore, we demonstrated that miR-149 directly targeted Forkhead box M1 (FOXM1), and FOXM1 was involved in the EMT induced by TGF- β 1 in A549 cells. Overexpression of FOXM1 restored EMT process inhibited by miR-149. Our work suggested that miR-149 might be an EMT suppressor in NSCLC cells.
Insights
MicroRNA-149 (miR-149) suppresses the epithelial-to-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) cells. This microRNA targets FOXM1, inhibiting cancer cell invasion and progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key regulators implicated in cancer progression.
- Epithelial-to-mesenchymal transition (EMT) is a critical process in non-small-cell lung cancer (NSCLC) cell invasion.
Purpose of the Study:
- To investigate the role of miR-149 in NSCLC cell EMT.
- To identify the molecular targets of miR-149 involved in EMT.
Main Methods:
- Correlation analysis of miR-149 expression with NSCLC cell invasiveness and EMT markers.
- In vitro experiments to assess miR-149's effect on EMT.
- Target validation using luciferase assays and Western blotting to confirm FOXM1 as a direct target.
- Rescue experiments with FOXM1 overexpression.
Main Results:
- miR-149 expression is downregulated in NSCLC and inversely correlated with invasive potential.
- miR-149 significantly inhibits EMT in NSCLC cells.
- miR-149 directly targets Forkhead box M1 (FOXM1).
- FOXM1 mediates TGF-β1-induced EMT, and its overexpression rescues miR-149's inhibitory effect.
Conclusions:
- miR-149 acts as a tumor suppressor by inhibiting EMT in NSCLC.
- The miR-149/FOXM1 axis is a critical pathway regulating NSCLC cell invasion and metastasis.
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