title: Evidence for the role of microRNA 374b in acquired cisplatin resistance in pancreatic cancer cells.
abstract: Recent evidence has implicated microRNAs (miRNAs) as potentially significant players in the acquisition of cancer-drug resistance in pancreatic and other cancers. To evaluate the potential contribution of miRNAs in acquired resistance to cisplatin in pancreatic cancer, we compared levels of more than 2000 human miRNAs in a cisplatin-resistant cell line (BxPC3-R) derived from parental (BxPC3) cells by step-wise exposure to increasing concentrations of the drug over more than 20 passages. The acquired drug resistance was accompanied by significant changes in the expression of 57 miRNAs, of which 23 were downregulated and 34 were upregulated. Employing a hidden Markov model (HMM) algorithm, we identified downregulation of miR-374b as likely being directly involved in acquisition of the drug-resistant phenotype. Consistent with this prediction, ectopic overexpression of miR-374b in the resistant BxPC3-R cells restored cisplatin sensitivity to levels approaching those displayed by the BxPC3 parental cells. The results are consistent with a growing body of evidence implicating miRNAs in acquired cancer-drug resistance and with the potential therapeutic value of these small regulatory RNAs in blocking and/or reversing the process.
authors.affiliation: School of Biology, Petit Institute of Bioengineering and BioSciences and Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, USA.|Laboratório de Biologia Cardiovascular, Faculdade de Ciências Médicas- UNICAMP, Prédio Vital, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: School of Biology, Petit Institute of Bioengineering and BioSciences and Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Mezencev
authors.affiliation: School of Biology, Petit Institute of Bioengineering and BioSciences and Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Matyunina
authors.affiliation: School of Biology, Petit Institute of Bioengineering and BioSciences and Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: McDonald
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000066630:Ectopic Gene Expression; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D059372:Nucleotide Motifs; D010190:Pancreatic Neoplasms / Q000235:genetics*; D056510:Position-Specific Scoring Matrices; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C587995:MIRN374 microRNA 374, human; D035683:MicroRNAs; D012333:RNA, Messenger; D002945:Cisplatin