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.
Highlights
Mature microRNAs are small endogenous noncoding RNAs consisting of 20,22 nucleotide duplexes
Down-regulation of miR-149 Expression in Head and neck squamous cell carcinoma (HNSCC) Tissues The expression of miR-149 in HNSCC and paired noncancerous matched tissue (NCMT) was determined by qRT-PCR analysis
Paired-t-test indicated a significant down-regulation of miR-149 expression in HNSCC tissue relative to the paired NCMT (p,0.001) (Fig. 1A)
Summary
Mature microRNAs (miRNAs) are small endogenous noncoding RNAs consisting of 20,22 nucleotide duplexes. The mature miRNAs complex with RISC and regulate target genes by mRNA cleavage through base pairing, by translational repression via binding to the 39 untranslated region (39-UTR) of the mRNA, or by deadenylating the mRNA [1]. Head and neck squamous cell carcinoma (HNSCC) includes SCC of oral cavity, oropharynx, hypopharynx and larynx. This disease is the 6th most common cancer worldwide [10]. Up-regulation of the oncogenic miRNAs, miR-184, miR-21 and miR-31, contributes to HNSCC carcinogenesis by targeting tumor suppressor genes [5,13,14]. Down-regulation of miR-205 has been found to be associated with the locoregional recurrence of HNSCC [16]. Preliminary screenings suggested alterations in other miRNAs occur during neoplastic process of HNSCC [5,14]
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