title: Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma.
abstract: Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as mitogen, motogen, and/or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects the expression of downstream functional genes has not yet been elucidated in detail. In the present study, we examined the expression of microRNA (miRNA), non-coding small RNA that regulate cell proliferation and functions by interfering with the translation of target mRNA, with or without HGF stimulation in HNSCC cell line HSC3. Among several miRNAs, in which the expression was altered after HGF stimulation, we focused on miR-200c and miR-27b, both of which were drastically downregulated after HGF stimulation. Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E-cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF stimulation. Expression of ST14/matriptase, an enzyme for extracellular matrix (ECM) degradation and HGF activation and a target mRNA for miR-27b, was drastically upregulated in the protein level after HGF stimulation, although it was not statistically altered in the mRNA level. These results suggest that miR-200c and miR-27b downregulated by HGF might play an important role in epithelial-mesenchymal transition mediated by ZEB1/E-cadherin and ECM degradation and HGF autoactivation mediated by ST14/matriptase, respectively. Altered expression of miRNA directly regulated by HGF might contribute enhanced progressive and invasive characteristics of HNSCC by regulating the translation of HGF-induced functional molecules.
authors: Division of Tumor Pathology, Department of Pathological Sciences, University of Fukui, Fukui, Japan.
authors: Dai
authors: D
authors: Susuki
authors: Sotai
authors: S
authors: Kimura
authors: Seiji
authors: S
authors: Naganuma
authors: Katsuki
authors: K
authors: Tsuchiyama
authors: Toshiaki
authors: T
authors: Tanaka
authors: Naomi
authors: N
authors: Kitamura
authors: Shigeharu
authors: S
authors: Fujieda
authors: Hiroshi
authors: H
authors: Itoh
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D017228:Hepatocyte Growth Factor; D012697:Serine Endopeptidases; C485596:ST14 protein, human