title: MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice.
abstract: MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression of their target genes. Numerous studies have shown that miRNAs are not only key regulators in important cellular processes but are also drivers in the development of many diseases, especially cancer. Estrogen receptor positive luminal B is the second most common but the least studied subtype of breast cancer. Only a few studies have examined the expression profiles of miRNAs in luminal B breast cancer, and their regulatory roles in cancer progression have yet to be investigated.
  
  
  
  In this study, using polyoma middle T antigen (PyMT) mice, a widely used luminal B breast cancer model, we profiled microRNA (miRNA) expression at four time points that represent different key developmental stages of cancer progression. We considered the expression of both miRNAs and messenger RNAs (mRNAs) at these time points to improve the identification of regulatory targets of miRNAs. By combining gene functional and pathway annotation with miRNA-mRNA interactions, we created a PyMT-specific tripartite miRNA-mRNA-pathway network and identified novel functional regulatory programs (FRPs).
  
  
  
  We identified 151 differentially expressed miRNAs with a strict dual nature of either upregulation or downregulation during the whole course of disease progression. Among 82 newly discovered breast-cancer-related miRNAs, 35 can potentially regulate 271 protein-coding genes based on their sequence complementarity and expression profiles. We also identified miRNA-mRNA regulatory modules driving specific cancer-related biological processes.
  
  
  
  In this study we profiled the expression of miRNAs during breast cancer progression in the PyMT mouse model. By integrating miRNA and mRNA expression profiles, we identified differentially expressed miRNAs and their target genes involved in several hallmarks of cancer. We applied a novel clustering method to an annotated miRNA-mRNA regulatory network and identified network modules involved in specific cancer-related biological processes.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogales-Cadenas
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Jhih-Rong
authors.initials: JR
authors.lastname: Lin
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Quanwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. zhengdong.zhang@einstein.yu.edu.|Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Room 353A, Bronx, NY, 10461, USA. zhengdong.zhang@einstein.yu.edu.
authors.forename: Zhengdong D
authors.initials: ZD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D005227:Fatty Acids; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Breast cancer; Cancer progression; Metastasis; MicroRNA; PyMT mouse model; Regulatory modules