RRC ID 63442
著者 Obayashi M, Yoshida M, Tsunematsu T, Ogawa I, Sasahira T, Kuniyasu H, Imoto I, Abiko Y, Xu D, Fukunaga S, Tahara H, Kudo Y, Nagao T, Takata T.
タイトル microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer.
ジャーナル Oncotarget
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.
巻・号 7(7)
ページ 8223-39
公開日 2016-2-16
DOI 10.18632/oncotarget.6972
PII 6972
PMID 26882562
PMC PMC4884988
MeSH Adult Aged Aged, 80 and over Apoptosis Blotting, Western Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / secondary Carcinoma, Squamous Cell / therapy Cell Proliferation Combined Modality Therapy DNA Methylation Epithelial-Mesenchymal Transition / genetics* Female Follow-Up Studies Gene Expression Regulation, Neoplastic* Head and Neck Neoplasms / genetics* Head and Neck Neoplasms / pathology Head and Neck Neoplasms / therapy Humans Immunoenzyme Techniques Lymphatic Metastasis Male MicroRNAs / genetics* Middle Aged Neoplasm Grading Neoplasm Invasiveness Neoplasm Staging Prognosis Protein Kinases / genetics Protein Kinases / metabolism* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Repressor Proteins / genetics Repressor Proteins / metabolism* Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured
IF 5.168
リソース情報
ヒト・動物細胞 HeLa 293T(RCB2202) HSC-2(RCB1945) A549