title: microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer.
abstract: Head and neck squamous cell carcinoma (HNSCC) has a high capacity for invasion. To identify microRNAs (miRNAs) that regulate HNSCC invasion, we compared miRNA expression profiles between a parent HNSCC cell line and a highly invasive clone. The miR-200 family and miR-203 were downregulated in the clone. Here we focused on the role of miR-203 in invasion and epithelial-mesenchymal transition (EMT) induction in HNSCC. miR-203 was downregulated during EMT induction. Moreover, ectopic overexpression of miR-203 suppressed the invasion and induced mesenchymal-epithelial transition (MET) in HNSCC cells. Interestingly, we identified NUAK family SNF1-like kinase 1 (NUAK1) as a novel target gene of miR-203 by cyclopedic analysis using anti-Ago2 antibody. Increased expression of NUAK1 was observed during EMT induction, and ectopic expression of miR-203 delayed EMT induction by suppressing NUAK1 expression. Moreover, NUAK1 overexpression promoted the invasion of HNSCC cells. Importantly, NUAK1 expression was well correlated with poor differentiation, invasiveness, and lymph node metastasis in HNSCC cases. Overall, miR-203 has a tumor-suppressing role in invasion and EMT induction by targeting NUAK1 in HNSCC, suggesting miR-203 as a potential new diagnostic and therapeutic target for the treatment of HNSCC.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Obayashi
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.|Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsunematsu
authors.affiliation: Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogawa
authors.affiliation: Department of Molecular Pathology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.affiliation: Department of Molecular Pathology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.affiliation: Department of Biochemistry, School of Dentistry at Matsudo, Nihon University, Chiba, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.|Institute of Environmental Systems Biology, Dalian Maritime University, Dalian, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fukunaga
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nagao
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C533896:MIRN200 microRNA, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012097:Repressor Proteins; D011494:Protein Kinases; C470845:NUAK1 protein, human
keywords: epithelial-mesenchymal transition (EMT); head and neck squamous cell carcinoma (HNSCC); invasion; microRNA (miRNA); microarray