hsa‑miR‑24 suppresses metastasis in nasopharyngeal carcinoma by regulating the c‑Myc/epithelial‑mesenchymal transition axis.

ONCOLOGY REPORTS(2018)

引用 10|浏览19
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摘要
Distant metastasis is the major contributor to treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). The lack of effective treatment strategies for metastatic NPC is the major cause for the low survival rate. Therefore, it is crucial to understand the molecular mechanisms underlying NPC metastasis and to identify potential biomarkers for targeted therapy. MicroRNA (miRNAs or miRs) have been shown to play an important role in tumorigenesis and metastasis. In the present study, we aimed to evaluate the significance of hsa-miR-24 in NPC metastasis. Significantly lower hsa-miR-24 levels were observed in NPC metastatic tumors and higher hsa-miR-24 levels were associated with longer progression-free and metastasis-free survival durations. hsa-miR-24 overexpression inhibited cell proliferation, invasion and migration. Using bioinformatics approaches together with functional luciferase reporter assays, we demonstrated that the c-Myc 3'-UTR was a direct target of hsa-miR-24 in regulating NPC metastasis. Protein profiling analysis revealed that a high c-Myc expression was inversely associated with metastasis-free overall survival and with epithelial-mesenchymal transition (EMT). Furthermore, the overexpression of hsa-miR-24 decreased NPC cell invasive ability induced by the overexpression of c-Myc, associated with EMT epithelial marker (E-cadherin) restoration. Thus, on the whole, the findings of this study demonstrate that hsa-miR-24 suppresses metastasis in NPC by regulating the c-Myc/EMT axis, suggesting that hsa-miR-24 may be used as a prognostic factor and as a novel target for the prevention of NPC metastasis.
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关键词
nasopharyngeal carcinoma,microRNA,c-Myc,epithelial-mesenchymal transition,metastasis
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