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Mechanical compression induces VEGFA overexpression in breast cancer via DNMT3A-dependent miR-9 downregulation

 Baek Gil Kim  ;  Ming-Qing Gao  ;  Suki Kang  ;  Yoon Pyo Choi  ;  Joo Hyun Lee  ;  Ji Eun Kim  ;  Hyun Ho Han  ;  Seong Gyeong Mun  ;  Nam Hoon Cho 
 Cell Death & Disease, Vol.8(3) : e2646, 2017 
Journal Title
 Cell Death & Disease 
Issue Date
Breast Neoplasms/genetics* ; Breast Neoplasms/pathology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methylation/genetics ; Disease Progression ; Down-Regulation/genetics* ; Female ; Fibroblasts/pathology ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; MCF-7 Cells ; Mechanotransduction, Cellular/genetics ; MicroRNAs/genetics* ; Promoter Regions, Genetic/genetics ; Signal Transduction/genetics ; Vascular Endothelial Growth Factor A/genetics*
Tumor growth generates mechanical compression, which may trigger mechanotransduction in cancer and stromal cells and promote tumor progression. However, very little is known about how compression stimulates signal transduction and contributes to tumor progression. In the present study, we demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation in the MDA-MB-231 and BT-474 breast cancer cell lines and in cancer-associated fibroblasts. The overexpression of miR-9 target genes (LAMC2, ITGA6, and EIF4E) was induced by miR-9 downregulation, which eventually enhanced vascular endothelial growth factors production. Demethylation and decompression could reverse compression-induced miR-9 downregulation and following overexpression of miR-9 target genes and VEGFA.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
강숙희(Kang, Suki) ORCID logo https://orcid.org/0000-0002-9957-3479
김백길(Kim, Baek Gil) ORCID logo https://orcid.org/0000-0001-6270-1433
조남훈(Cho, Nam Hoon) ORCID logo https://orcid.org/0000-0002-0045-6441
한현호(Han, Hyun Ho) ORCID logo https://orcid.org/0000-0002-6268-0860
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