title: MEK Inhibitor Suppresses Expression of the miR-17-92 Cluster with G1-Phase Arrest in HT-29 Human Colon Cancer Cells and MIA PaCa-2 Pancreatic Cancer Cells.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs, and the deregulated expression of miRNAs is associated with tumor development. Among these, the miR-17-92 cluster, including six mature miRNAs, is known as an oncogenic miRNA cluster because expression of the miR-17-92 cluster is frequently elevated in a variety of malignant tumors.
  
  
  
  We investigated whether a mitogen-activated protein kinase kinase (MEK) inhibitor, PD0325901, suppresses expression of the miR-17-92 cluster in HT-29 human colon cancer cells and MIA PaCa-2 pancreatic cancer cells.
  
  
  
  PD0325901 inhibited cell growth with G1-phase arrest and suppressed expression of the miR-17-92 cluster. Furthermore, phosphatase and tensin homolog (PTEN), which is a target molecule of the miR-17-92 cluster, was up-regulated by PD0325901. The exogenous expression of miR-17 slightly, but significantly reduced G1-phase arrest by PD0325901.
  
  
  
  These results raise the possibility that a MEK inhibitor causes G1-phase arrest, at least partially, through suppression of the miR-17-92 cluster.
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tomosugi
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan ysowa@koto.kpu-m.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
mesh_terms: D001549:Benzamides / Q000737:chemistry; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000737:chemistry; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000737:chemistry; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D062085:RNA, Long Noncoding
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C506614:mirdametinib; D004159:Diphenylamine; D020930:MAP Kinase Kinase Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: G1-phase arrest; MEK inhibitor; PTEN; miR-17-92 cluster; microRNA