title: The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells.
abstract: S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter.
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA; University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: Melania E
authors.initials: ME
authors.lastname: Mercado-Pimentel
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA; Cancer Biology Graduate Program, University of Arizona, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Onyeagucha
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Molecular and Cell Biology, University of Arizona, USA.
authors.forename: Angel C
authors.initials: AC
authors.lastname: Pimentel
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA; University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Jandova
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA; Cancer Biology Graduate Program, University of Arizona, USA; University of Arizona Cancer Center, Tucson, AZ, USA. Electronic address: mnelson@pathology.arizona.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Nelson
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D030541:Databases, Genetic; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D002135:Calcium-Binding Proteins; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C115460:RECK protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C103003:S100P protein, human; D018808:Transcription Factor AP-1
keywords: AP-1; Colon cancer; Inflammation; Metastasis; RAGE; RECK; TCGA; miR-21; microRNAs