title: miR-17-5p inhibitor enhances chemosensitivity to gemcitabine via upregulating Bim expression in pancreatic cancer cells.
abstract: BACKGROUND
  miR-17-5p is reported to be overexpressed in pancreatic cancer, and it plays an important role in carcinogenesis and cancer progression. Gemcitabine is the standard first-line chemotherapeutic agent for pancreatic cancer, however the chemoresistance limits the curative effect.
  
  
  OBJECTIVE
  In the present study, we investigated whether inhibition of miR-17-5p could enhance chemosensitivity to gemcitabine in pancreatic cancer cells.
  
  
  METHODS
  miR-17-5p inhibitor was transfected to pancreatic cancer cell lines Panc-1 and BxPC3, and then cell proliferation, cell apoptosis, caspase-3 activation, and chemosensitivity to gemcitabine were measured in vitro.
  
  
  RESULTS
  Our data showed that Panc-1 and BxPC3 cells transfected with miR-17-5p inhibitor showed growth inhibition, spontaneous apoptosis, higher caspase-3 activation, and increased chemosensitivity to gemcitabine. In addition, miR-17-5p inhibitor upregulated Bim protein expression in a dose-dependent manner without changing the Bim mRNA level, and it increased the activity of a luciferase reporter construct containing the Bim-3' untranslated region.
  
  
  CONCLUSIONS
  These results prove that miR-17-5p negatively regulates Bim at the posttranscriptional level. We suggest that miR-17-5p inhibitor gene therapy would be a novel approach to chemosensitization for human pancreatic cancer.
authors.affiliation: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People's Republic of China.
authors.forename: Hai-Jiao
authors.initials: HJ
authors.lastname: Yan
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Liu
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Jing-Ting
authors.initials: JT
authors.lastname: Jiang
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Wu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C524941:MIRN17 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D053148:Caspase 3; D000093542:Gemcitabine