title: Dual-receptor (EGFR and c-MET) inhibition by tumor-suppressive miR-1 and miR-206 in head and neck squamous cell carcinoma.
abstract: Our studies of microRNA (miRNA) expression signatures have shown that microRNA-1 (miR-1) and microRNA-206 (miR-206) were downregulated in head and neck squamous cell carcinoma (HNSCC) clinical specimens. The seed sequences of these miRNAs are identical, suggesting that the identification of the molecular targets regulated by miR-1 and miR-206 will provide new insights into novel mechanisms of HNSCC pathogenesis. Our present data showed that restoration of miR-1 and miR-206 significantly inhibited HNSCC cells' aggressiveness. A combination of gene expression data and in silico analysis revealed that several pathways ('pathway in cancer', 'focal adhesion pathway', 'MAPK signaling pathway', 'regulation of actin cytoskeleton pathway' and 'ECM-receptor interaction pathway') were regulated by miR-1 and miR-206. Among them, we found that two growth factor receptors, epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET), were directly regulated by both miR-1 and miR-206 in HNSCC cells. Also, downstream oncogenic signaling of these receptors was reduced by restoration of miR-1 or miR-206 expression. Moreover, overexpression of EGFR and c-MET was observed in HNSCC clinical specimens. The identification of targets modulated by tumor-suppressive miR-1 and miR-206 may lead to a better understanding of molecular pathogenesis of HNSCC.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koshizuka
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Hanazawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fukumoto
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kikkawa
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mataki
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Keiko
authors.identifier: http://orcid.org/0000-0001-6738-7906
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C544547:MIRN1 microRNA, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met