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miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma (OSCC) invasion and metastasis.
MedLine Citation:
PMID:  24335959     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
microRNAs 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 OSCC patients. 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 ERK1/2 activation and MMP2/9 levels and activities. In clinical specimens of OSCC, 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 OSCC 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.
Authors:
Lu-Hai Wang; Wei-Chieh Huang; Shih-Hsuan Chan; Te-Hsuan Jang; Jer-Wei Chang; Ying-Chin Ko; Tzu-Chen Yen; Shang-Lun Chiang; Wei-Fan Chiang; Tien-Yu Shieh; Chun-Ta Liao; Jyh-Lyh Juang; Hsueh-Chun Wang; Ann-Joy Cheng; Ya-Ching Lu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-12
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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