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

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.

MiR-24-3p as a prognostic indicator for multiple cancers: from a meta-analysis view

“…The overall sample size is 1518 patients coming from 25 to 247 which from 4 countries. Among these studies, several types of cancer include lung cancer ( n =3) [ 33–35 ], hepatocellular carcinoma ( n =2) [ 36 , 37 ], colorectal cancer ( n =2) [ 29 , 38 ], nasopharyngeal carcinoma ( n =2) [ 39 , 40 ], osteosarcoma ( n =1) [ 41 ], ALL ( n =1) [ 42 ], AML ( n =1) [ 42 ], advanced gastric cancer ( n =1) [ 28 ], esophageal cancer ( n =1) [ 43 ], and head and neck squamous cell carcinoma ( n =1) [ 44 ]. As for OS, RFS, and DFS, there were seven studies directly provide HRs and its 95% CI [ 28 , 29 , 35–39 ].…”

MiR-24-3p and various cancers: From a meta-analysis view

“…Among these studies, several types of cancer include lung cancer (n = 3) [33][34][35], hepatocellular carcinoma (n = 2) [36,37], colorectal cancer (n = 2) [29,38], nasopharyngeal carcinoma (n = 2) [39,40], osteosarcoma (n = 1) [41], ALL (n = 1) [42], AML (n = 1) [42], advanced gastric cancer (n = 1) [28], esophageal cancer (n = 1) [43], head and neck squamous cell carcinoma (n = 1) [44]. As for OS, RFS and DFS, there were seven studies directly provide HRs and its 95% CI [28,29,[35][36][37][38][39]. In addition, the remaining eight studies only provided Kaplan-Meier curves [28,33,34,[40][41][42][43][44].…”

Prognostic significance of microRNA miR-24 in cancers: a meta-analysis

“…After screening the full text of these articles, 15 articles were excluded. Eventually, 15 articles published between 2012 and 2018 were included in the study [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The study flow chart is shown in Figure 1.…”

“…Studies have revealed that miR-24 involves in tumor cell proliferation, differentiation, invasion, and metastasis by regulating numerous genes, such as PTEN, TRIM11, SOX7, PRKCH, and P16 [5][6][7][8][9]. Recently, abnormal miR-24 expression has been reported to be correlated with the prognosis and clinical characteristics in tumors, including gastric cancer (GC), lung cancer (LC), colorectal cancer (CRC), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), and tongue squamous cell carcinoma (TSCC) [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Most studies reported that high miR-24 expression predicted poor prognosis, while several other studies shown the opposite view.…”