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MicroRNA‐196a promotes an oncogenic effect in head and neck cancer cells by suppressing annexin A1 and enhancing radioresistance
Author(s) -
Suh YaeEun,
Raulf Nina,
Gäken Joop,
Lawler Katherine,
Urbano Teresa Guerrero,
Bullenkamp Jessica,
Gobeil Stéphane,
Huot Jacques,
Odell Eddy,
Tavassoli Mahvash
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29397
Subject(s) - radioresistance , gene knockdown , head and neck squamous cell carcinoma , cancer research , microrna , biology , head and neck cancer , downregulation and upregulation , cell growth , annexin , cell culture , medicine , pathology , radiation therapy , gene , biochemistry , genetics
Radiotherapy is a major treatment modality for head and neck squamous cell carcinoma (HNSCC). Up to 50% of patients with locally advanced disease relapse after radical treatment and there is therefore a need to develop predictive bomarkers for clinical use that allow the selection of patients who are likely to respond. MicroRNA (miRNA) expression profiling of a panel of HNSCC tumours with and without recurrent disease after surgery and radiotherapy detected miR‐196a as one of the highest upregulated miRNAs in the poor prognostic group. To further study the role of miR‐196a, its expression was determined in eight head and neck cancer cell lines. Overexpression of miR‐196a in HNSCC cells, with low endogenous miR‐196a expression, significantly increased cell proliferation, migration and invasion, and induced epithelial to mesenchymal transition. Conversely, miR‐196a knockdown in cells with high endogenous expression levels significantly reduced oncogenic behaviour. Importantly, overexpression of miR‐196a increased radioresistance of cells as measured by gamma H2AX staining and MTT survival assay. Annexin A1 (ANXA1), a known target of miR‐196a, was found to be directly modulated by miR‐196a as measured by luciferase assay and confirmed by Western blot analysis. ANXA1 knockdown in HNSCC exhibited similar phenotypic effects to miR‐196a overexpression, suggesting the oncogenic effect of miR‐196a may at least be partly regulated through suppression of ANXA1. In conclusion, this study identifies miR‐196a as a potential important biomarker of prognosis and response of HNSCC to radiotherapy. Furthermore, our data suggest that miR‐196a and/or its target gene ANXA1 could represent important therapeutic targets in HNSCC.