MiRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis

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题名:	MiRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis
作者:	王陸海;Huang, Wei-Chieh;Chan, Shih-Hsuan;Jang, Te-Hsuan;Chang, Jer-Wei;Ko, Ying-Chin;Yen, Tzu-Chen;Chiang, Shang-Lun;Chiang, Wei-Fan;Shieh, Tien-Yu;Liao, Chun-Ta;Juang, Jyh-Lyh;Wang, Hsueh-Chun;Cheng, Ann-Joy;Lu, Ya-Ching;Wang, Lu-Hai
贡献者:	生醫理工學院生命科學系
关键词:	Adaptor Proteins, Signal Transducing - genetics;Adaptor Proteins, Signal Transducing - metabolism;Animals;Antineoplastic agents;Biological and medical sciences;Biomarkers, Tumor;Carcinoma, Squamous Cell - genetics;Carcinoma, Squamous Cell - mortality;Carcinoma, Squamous Cell - pathology;Cell Cycle Proteins - genetics;Cell Cycle Proteins - metabolism;Cell Line, Tumor;Cell Movement - genetics;Disease Models, Animal;Focal Adhesion Kinase 1 - genetics;Focal Adhesion Kinase 1 - metabolism;Focal Adhesions - genetics;Gene Expression Regulation, Neoplastic;Humans;Lung Neoplasms - genetics;Lung Neoplasms - secondary;MAP Kinase Signaling System;Matrix Metalloproteinase 2 - metabolism;Matrix Metalloproteinase 9 - metabolism;Medical sciences;Mice;MicroRNAs - genetics;MicroRNAs - metabolism;Mouth Neoplasms - genetics;Mouth Neoplasms - mortality;Mouth Neoplasms - pathology;Multiple tumors. Solid tumors. Tumors in childhood (general aspects);Neoplasm Invasiveness;Neoplasm Metastasis;Otorhinolaryngology. Stomatology;Paxillin - metabolism;Pharmacology. Drug treatments;Proteolysis;Receptor, Epidermal Growth Factor - metabolism;RNA Interference;Signal Transduction;Tumors;Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
日期:	2014-02-01
上传时间:	2026-04-23 11:13:25 (UTC+8)
出版者:	American Association for Cancer Research Inc.;Philadelphia, PA: American Association for Cancer Research (AACR)
摘要:	摘要： AbstractMicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein—coupled receptor kinase-interacting protein 1 (GIT1)—as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p–mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal–regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. Cancer Res; 74(3); 751–64. ©2013 AACR. 其他題名： Cancer Res 出版者： Philadelphia, PA: American Association for Cancer Research (AACR) 出版日期： 2014-02-01 出處： Cancer Research, 2014-02, Vol.74 (3), p.751-764 版權： 2015 INIST-CNRS 識別號： ISSN: 0008-5472 識別號： ISSN: 1538-7445 識別號： EISSN: 1538-7445 識別號： DOI: 10.1158/0008-5472.can-13-1297 識別號： PMID: 24335959 識別號： CODEN: CNREA8
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