title: MicroRNA-196a promotes an oncogenic effect in head and neck cancer cells by suppressing annexin A1 and enhancing radioresistance.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Yae-Eun
authors.initials: YE
authors.lastname: Suh
authors.affiliation: Department of Molecular Oncology, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Raulf
authors.affiliation: Department of Haematological Medicine, King's College London, the Rayne Institute, London, SE5 9NU, UK.
authors.forename: Joop
authors.initials: J
authors.lastname: Gäken
authors.affiliation: Division of Cancer Studies and Institute of Mathematical and Molecular Biomedicine, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lawler
authors.affiliation: Clinical Oncology Department, Lambeth Wing, St Thomas' Hospital, Westminster, Bridge, Road, UK, London, SE1, 7EH.
authors.forename: Teresa Guerrero
authors.initials: TG
authors.lastname: Urbano
authors.affiliation: Department of Molecular Oncology, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bullenkamp
authors.affiliation: Centre Hospitalier De L'université Laval (CHUL, 2705, Boulevard Laurier, R-4720 Québec, G1V 4G2, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobeil
authors.affiliation: Centre De Recherche Du CHU De Québec Et Centre De Recherche En Cancérologie De L'université Laval, 9 Rue McMahon, Québec, G1R 2J6, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Huot
authors.affiliation: Department of Molecular Oncology, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Eddy
authors.initials: E
authors.lastname: Odell
authors.affiliation: Department of Molecular Oncology, King's College London, Guy's Hospital Campus, London, SE1 1UL, UK.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Tavassoli
mesh_terms: D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D058750:Epithelial-Mesenchymal Transition / Q000528:radiation effects; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D011379:Prognosis; D011836:Radiation Tolerance
chemical_list: D017305:Annexin A1; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: MicroRNA-196a; annexin A1; biomarkers; head and neck squamous cell carcinoma; radiosensitivity