title: Sweating the small stuff: microRNAs and genetic changes define pancreatic cancer.
abstract: MicroRNAs (miRNAs) are 18- to 22-nucleotide-long, single-stranded, noncoding RNAs that regulate important biological processes including differentiation, proliferation, and response to cellular stressors such as hypoxia, nutrient depletion, and traversion of the cell cycle by controlling protein expression within the cell. Many investigators have profiled cancer tissue and serum miRNAs to identify potential therapeutic targets, understand the pathways involved in tumorigenesis, and identify diagnostic tumor signatures. In the setting of pancreatic cancer, obtaining pancreatic tissue is invasive and impractical for early diagnosis. Several groups have profiled miRNAs that are present in the blood as a means to diagnose tumor progression and predict prognosis/survival or drug resistance. Several miRNA signatures found in pancreatic tissue and the peripheral blood, as well as the pathways that are associated with pancreatic cancer, are reviewed here in detail. Three miRNA biomarkers (miR-21, miR-155, and miR-200) have been repetitively identified in both pancreatic cancer tissue and patients' blood. Those miRNAs regulate and are regulated by the central genetic and epigenetic changes observed in pancreatic cancer including p53, transforming growth factor β, p16(INK4A), BRCA1/2, and Kras. These miRNAs are involved in DNA repair, cell cycle, and cell invasion and also play important roles in promoting metastases.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Siuwah
authors.initials: S
authors.lastname: Tang
authors.forename: Jillian
authors.initials: J
authors.lastname: Bonaroti
authors.forename: Sebnem
authors.initials: S
authors.lastname: Unlu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D042241:Early Diagnosis; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011379:Prognosis
chemical_list: C524942:MIRN155 microRNA, human; C533896:MIRN200 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs