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

Su,Bojin; Xu,Tao; Bruce,Jeff P.; Yip,Kenneth W.; Zhang,Ning; Huang,Zeli; Zhang,Guoyi; Liu,Fei‑Fei; Liang,Jiyong; Yang,Huiling; Claret,François X.

doi:10.3892/or.2018.6690

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

Authors:
- Bojin Su
- Tao Xu
- Jeff P. Bruce
- Kenneth W. Yip
- Ning Zhang
- Zeli Huang
- Guoyi Zhang
- Fei‑Fei Liu
- Jiyong Liang
- Huiling Yang
- François X. Claret
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Affiliations: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, , Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada, Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: September 7, 2018 https://doi.org/10.3892/or.2018.6690
Pages: 2536-2546
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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