title: A 22q11.2 amplification in the region encoding microRNA-650 correlates with the epithelial to mesenchymal transition in breast cancer primary cultures of Mexican patients.
abstract: Breast cancer ranks first in incidence and mortality in working age women. Cancer initiation and progression relies on accumulation of genetic and epigenetic aberrations that alter cellular processes, among them, epithelial to mesenchymal transition (EMT) denotes particularly aggressive neoplasias given its capacity to invade and metastasize. Several microRNAs (miRNA) have been found able to regulate gene expression at the core of EMT. In this study, the Affymetrix CytoScan HD array was used to analyze three different primary tumor cell isolates from Mexican breast cancer patients. We found an amplification in band 22q11.2 shared by the three samples, in the region that encodes miRNA-650. Overexpression of this miRNA has been associated with downregulation of tumor suppressors ING4 and NDRG2, which have been implicated in cancer progression. Using the Pathway Linker platform the ING4 and NDRG2 interaction networks showed a significant association with signaling pathways commonly deregulated in cancer. Also, several studies support their participation in the EMT. Supporting the latter, we found that the three primary isolates were E-cadherin negative, vimentin positive, presented a cancer stem cell-like phenotype CD44+CD24-/low and were invasive in Transwell invasion assays. This evidence suggests that the gain of region 22q11.2 contributes to trigger EMT. This is the first evidence linking miR-650 and breast cancer.
authors.affiliation: Research Unit on Virology and Cancer, Children's Hospital of Mexico 'Federico Gómez', C.P. 06720 Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Lango-Chavarría
authors.affiliation: Research Unit on Virology and Cancer, Children's Hospital of Mexico 'Federico Gómez', C.P. 06720 Mexico City, Mexico.
authors.forename: G K
authors.initials: GK
authors.lastname: Chimal-Ramírez
authors.affiliation: Medical Research Unit on Human Genetics, Pediatric's Hospital, Mexican Institute of Social Security XXI Century, Del. Cuauhtemoc, C.P. 06720 Mexico City, Mexico.
authors.forename: M E
authors.initials: ME
authors.lastname: Ruiz-Tachiquín
authors.affiliation: Research Unit on Virology and Cancer, Children's Hospital of Mexico 'Federico Gómez', C.P. 06720 Mexico City, Mexico.
authors.forename: N A
authors.initials: NA
authors.lastname: Espinoza-Sánchez
authors.affiliation: Research Unit on Virology and Cancer, Children's Hospital of Mexico 'Federico Gómez', C.P. 06720 Mexico City, Mexico.
authors.forename: M C
authors.initials: MC
authors.lastname: Suárez-Arriaga
authors.affiliation: Research Unit on Virology and Cancer, Children's Hospital of Mexico 'Federico Gómez', C.P. 06720 Mexico City, Mexico.
authors.forename: E M
authors.initials: EM
authors.lastname: Fuentes-Pananá
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D002892:Chromosomes, Human, Pair 22; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008800:Mexico; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; C550124:MIRN650 microRNA, human; D035683:MicroRNAs; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins