title: Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer.
abstract: MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction.
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Kaylyn L
authors.initials: KL
authors.lastname: Devlin
authors.affiliation: Asuragen Incorporated, Austin, Texas, United States of America.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sanford
authors.affiliation: Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Harrison
authors.affiliation: Asuragen Incorporated, Austin, Texas, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: LeBourgeois
authors.affiliation: Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Lashinger
authors.affiliation: Asuragen Incorporated, Austin, Texas, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mambo
authors.affiliation: Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D031204:Caloric Restriction; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000178:diet therapy / Q000235:genetics* / Q000401:mortality; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden
chemical_list: C533896:MIRN200 microRNA, human; C555600:MIRN200 microRNA, rat; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; D015127:9,10-Dimethyl-1,2-benzanthracene