title: Mechanical compression induces VEGFA overexpression in breast cancer via DNMT3A-dependent miR-9 downregulation.
abstract: 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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Gao
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Han
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Seong Gyeong
authors.initials: SG
authors.lastname: Mun
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, South Korea.|Global 5-5-10 System Biology, Yonsei University, Seoul, South Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D040542:Mechanotransduction, Cellular / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C000717967:DNMT3A protein, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A