title: MicroRNA-27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling.
abstract: The non-receptor tyrosine kinase c-Src is frequently activated during progression of colon cancers. In this study, we found that among the c-Src-regulated microRNAs (miRNAs), miR-27b is also repressed by activation of K-Ras/H-Ras. Inhibitor studies suggested that the phosphatidylinositol 3-kinase pathway is involved in the repression of miR-27b. MicroRNA-27b was repressed in various colon cancer cell lines and tumor tissues. Re-expression of miR-27b in human colon cancer HCT116 cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified ARFGEF1 and paxillin as novel targets of miR-27b, and found that miR-27b-mediated regulation of ARFGEF1 is crucial for controlling anchorage-independent growth, and that of paxillin is important for controlling cell adhesion and invasion. Re-expression of miR-27b suppressed the activation of c-Src induced by integrin-mediated cell adhesion, suggesting that repression of miR-27b may contribute to c-Src activation in cancer cells. These findings show that miR-27b functions as a tumor suppressor by controlling ARFGEF1 and the paxillin/c-Src circuit at focal adhesions.
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Matsuyama
authors.affiliation: DNA-Chip Developmental Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.|Division of Microbiology and Oncology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan.
authors.forename: Chitose
authors.initials: C
authors.lastname: Oneyama
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C119087:ARFGEF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C496061:PXN protein, human; D051419:Paxillin; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: ARFGEF1; Adhesion; Src; miRNA; paxillin