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MicroRNAs (miRNAs) play important roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). A genetic polymorphism (rs2292832, C>T) has been recently identified in the precursor of  miR-149 ; nevertheless its clinicopathological implications remain obscure. In this study, we showed that  miR-149  is down-regulated in HNSCC compared to normal mucosa and this is associated with a poorer patient survival. In addition, HNSCC patients with the T/T genotype have more advanced tumors and a worse prognosis. Multivariate analysis indicated that patients carried the T/T genotype have a 2.81-fold (95% CI: 1.58–4.97) increased risk of nodal metastasis and 1.66-fold (95% CI: 1.05–2.60) increased risk of mortality compared to other groups. T/T genotype also predicted the worse prognosis of buccal mucosa carcinoma subset of HNSCC.  In vitro  analysis indicated that exogenous  miR-149  expression reduces the migration of HNSCC cells. Moreover, HNSCC cell subclones carrying the pri- mir-149  sequence containing the T variant show a low processing efficacy when converting the pre- mir-149  to mature  miR-149 . These findings suggest that  miR-149  suppresses tumor cell mobility, and that the pre- mir-149  polymorphism may affect the processing of  miR-149 , resulting in a change in the abundance of the mature form miRNA, which, in turn, modulates tumor progression and patient survival.

plos one

The Association between Genetic Polymorphism and the Processing Efficiency of miR-149 Affects the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma