title: Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.
abstract: The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.
authors: The University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, United States of America; Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, United States of America.
authors: José L
authors: JL
authors: Muñoz-Rodríguez
authors: The University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, United States of America.
authors: Lukas
authors: L
authors: Vrba
authors: The University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, United States of America; Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, United States of America.
authors: Bernard W
authors: BW
authors: Futscher
authors: Department of Epidemiology and Biostatistics, The Mel & Enid Zuckerman College of Public Health, The University of Arizona, Tucson, AZ, United States of America.
authors: Chengcheng
authors: C
authors: Hu
authors: Department of Surgery, Maricopa Medical Center, Phoenix, AZ, United States of America.
authors: Ian K
authors: IK
authors: Komenaka
authors: Instituto Tecnológico de Sonora, Ciudad Obregón, México.
authors: Maria Mercedes
authors: MM
authors: Meza-Montenegro
authors: Departamento de Investigaciones Científicas y Tecnológicas, Universidad de Sonora, Hermosillo, México.
authors: Luis Enrique
authors: LE
authors: Gutierrez-Millan
authors: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
authors: Adrian
authors: A
authors: Daneri-Navarro
authors: Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, United States of America.
authors: Patricia A
authors: PA
authors: Thompson
authors: Department of Family & Preventive Medicine, University of California San Diego, La Jolla, CA, United States of America.
authors: Maria Elena
authors: ME
authors: Martinez
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D049590:Postpartum Period / Q000235:genetics*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs