407012

MIR24-1

Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Previous studied have shown dysregulation of miR-24 in a variety of tumors. However, the roles of miR-24 in human bladder cancer have not been well clarified. Therefore, we investigated the biological functions and molecular mechanisms of miR-24 in human bladder cancer cell lines, evaluating whether it could be a therapeutic biomarker of bladder cancer in the future. In our study, we found that miR-24 is downregulated in human bladder cancer cell lines. Moreover, the low level of miR-24 was associated with increased expression of CARMA3 in bladder cancer cells. Upregulation of miR-24 significantly inhibited proliferation, arrested cell cycle and induced apoptosis in bladder cancer cells. In addition, invasion and epithelial to mesenchymal transition (EMT) of bladder cancer cells was suppressed by overexpressing miR-24. Bioinformatics analysis predicted that the CARMA3 was a potential target gene of miR-24. Further study by luciferase reporter assay demonstrated that miR-24 could directly target CARMA3. Overexpression of CARMA3 in bladder cancer cells transfected with miR-24 mimic partially reversed the inhibitory effect of miR-24. In conclusion, miR-24 inhibited cell proliferation, invasion and EMT in bladder cancer cells by downregulation of CARMA3, and that downregulation of CARMA3 was essential for the miR-24-inhibited cell proliferation, invasion and EMT in bladder cancer cells.

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 hsamiR24 in NPC metastasis. Significantly lower hsamiR24 levels were observed in NPC metastatic tumors and higher hsamiR24 levels were associated with longer progressionfree and metastasisfree survival durations. hsamiR24 overexpression inhibited cell proliferation, invasion and migration. Using bioinformatics approaches together with functional luciferase reporter assays, we demonstrated that the cMyc 3'UTR was a direct target of hsamiR24 in regulating NPC metastasis. Protein profiling analysis revealed that a high cMyc expression was inversely associated with metastasisfree overall survival and with epithelialmesenchymal transition (EMT). Furthermore, the overexpression of hsamiR24 decreased NPC cell invasive ability induced by the overexpression of cMyc, associated with EMT epithelial marker (Ecadherin) restoration. Thus, on the whole, the findings of this study demonstrate that hsamiR24 suppresses metastasis in NPC by regulating the cMyc/EMT axis, suggesting that hsamiR24 may be used as a prognostic factor and as a novel target for the prevention of NPC metastasis.