Open AccessRegulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma
Author(s) -
Susuki Dai,
Kimura Sotai,
Naganuma Seiji,
Tsuchiyama Katsuki,
Tanaka Toshiaki,
Kitamura Naomi,
Fujieda Shigeharu,
Itoh Hiroshi
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02096.x
Subject(s) - hepatocyte growth factor , downregulation and upregulation , head and neck squamous cell carcinoma , microrna , microbiology and biotechnology , cancer research , small interfering rna , cell growth , biology , epithelial–mesenchymal transition , chemistry , cell culture , transfection , receptor , cancer , gene , head and neck cancer , biochemistry , genetics
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. ( Cancer Sci 2011; 102: 2164–2171)