title: Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family.
abstract: Kindlin 2, as a focal adhesion protein, controls integrin activation and regulates Wnt signaling in an integrin-binding independent manner. However, the association of Kindlin 2 with cancer-related microRNAs is unknown. Here, we report that Kindlin 2 markedly downregulates the expression of miR-200 family by inducing CpG island hypermethylation. Mechanistically, Kindlin 2 forms a complex with DNMT3A in the cell nucleus and the two proteins co-occupy the promoter of miRNA-200b. Functionally, repression of miR-200b is required for Kindlin 2-induced breast cancer cell invasion and tumor formation. Our data indicate that Kindlin 2 plays a novel role in epigenetic repression of miR-200 family, a mechanism that promotes breast cancer invasion.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education of China, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: Junzhou
authors.initials: J
authors.lastname: Wu
authors.forename: Lizhao
authors.initials: L
authors.lastname: Guan
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Zhan
authors.forename: Yunling
authors.initials: Y
authors.lastname: Wang
authors.forename: Weigang
authors.initials: W
authors.lastname: Fang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*
chemical_list: C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; C477322:FERMT3 protein, human; C533896:MIRN200 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNA methyltransferase; Kindlins; MicroRNA-200 family; breast cancer