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 |