BackgroundLet-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a.MethodsThe expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells.ResultsOur study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3′UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells.ConclusionLet-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0462-8) contains supplementary material, which is available to authorized users.
Matrix metalloproteinase-14 (MMP-14) has been demonstrated to play an important role in tumor progression. The aim of this study was to analyze the correlation between MMP-14 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). Immunohistochemical staining for MMP-14 protein was performed in 104 patients with NSCLC. High levels of MMP-14 protein were positively correlated with the status of clinical stage (I-II vs. III-IV; P < 0.001), N classification (N0-N1 vs. N2-N3; P < 0.001), distant metastasis (no vs. yes; P = 0.014), and differentiated degree (high vs. low or undifferentiated; P = 0.001). The patients with higher MMP-14 expression of protein had shorter survival time than patients with low MMP-14 expression. Multivariate analysis indicated that the level of MMP-14 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with NSCLC. In conclusion, MMP-14 is a potential unfavorable prognostic factor for patients with NSCLC.
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