title: miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway.
abstract: Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.
  
  
  
  miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis.
  
  
  
  miR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation.
  
  
  
  This study contributes to the understanding of the AMPs' mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy.
authors.affiliation: Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: United Graduate School of Agricultural Sciences, Graduate School of Agricultural Science, Iwate University, Morioka, Iwate, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: School of Environment and Life Sciences, University of Salford, Salford, UK.
authors.forename: Marija
authors.initials: M
authors.lastname: Krstic-Demonacos
authors.affiliation: Division of Pharmacy and Optometry, Faculty of Biology Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Demonacos
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Animal Research Center, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isogai
authors.affiliation: Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.affiliation: Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan. homeiso2006@yahoo.co.jp.
authors.forename: Emiko
authors.initials: E
authors.lastname: Isogai
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D019718:Receptors, CXCR4 / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; C527276:CXCR4 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D019718:Receptors, CXCR4; D054804:Cathelicidins
keywords: Cationic Antimicrobial Peptides and CXCR4; HCT116 cells; miR-663a