title: The association between genetic polymorphism and the processing efficiency of miR-149 affects the prognosis of patients with head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Dentistry, National Yang-Ming University Hospital, I-Lan, Taiwan.
authors.forename: Hsi-Feng
authors.initials: HF
authors.lastname: Tu
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.forename: Che-Lun
authors.initials: CL
authors.lastname: Chang
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Yang
authors.forename: En-Hao
authors.initials: EH
authors.lastname: Yu
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Lin
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011379:Prognosis; D012044:Regression Analysis; D012306:Risk; D016896:Treatment Outcome
chemical_list: C551557:MIRN149 microRNA, human; D035683:MicroRNAs