microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer
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Mariko Obayashi1,*, Maki Yoshida1,9,*, Takaaki Tsunematsu2, Ikuko Ogawa3, Tomonori Sasahira4, Hiroki Kuniyasu4, Issei Imoto5, Yoshimitsu Abiko6, Dan Xu7,8, Saori Fukunaga7, Hidetoshi Tahara7, Yasusei Kudo2, Toshitaka Nagao9, Takashi Takata1
1Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
2Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
3Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan
4Department of Molecular Pathology, Nara Medical University School of Medicine, Nara, Japan
5Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
6Department of Biochemistry, School of Dentistry at Matsudo, Nihon University, Chiba, Japan
7Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
8Institute of Environmental Systems Biology, Dalian Maritime University, Dalian, China
9Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan
*These authors have contributed equally to this work
Takashi Takata, e-mail: email@example.com
Keywords: invasion, microRNA (miRNA), epithelial-mesenchymal transition (EMT), head and neck squamous cell carcinoma (HNSCC), microarray
Received: August 02, 2015 Accepted: January 01, 2016 Published: January 22, 2016
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.
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