title: miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro.
abstract: Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
authors.affiliation: Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Lv
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiao
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Qing
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.forename: Xiuying
authors.initials: X
authors.lastname: Cui
authors.forename: Tianxin
authors.initials: T
authors.lastname: Lin
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
authors.forename: Fengyan
authors.initials: F
authors.lastname: Yu
mesh_terms: D023102:Anoikis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D055513:Connective Tissue Growth Factor; C075397:RHOG protein, human; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins
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