BACKGROUND: Alterations in the expression level of miR-495 were recently observed in various tumours. Medulloblastoma is the most common malignant brain tumour in children. However, the clinical significance of miR-495 in medulloblastomas remains unclear. METHODS: The expression levels of miR-495 was examined in 62 archival formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens using TaqMan Real-time Quantitative PCR arrays. Immunohistochemistry was used to determine the expression of Gfi1 in medulloblastoma tissues, and a luciferase reporter assay was carried out to confirm whether Gfi1 is a direct target of miR-495. RESULTS: MiR-495 expression is repressed in medulloblastoma samples compared with normal cerebellum tissues. Furthermore, patients with a low level of miR- 495 showed significantly poorer survival, as determined by the log-rank test (P = 0.033). The multivariate analysis results showed that the miR-495 expression levels were an independent predictor of overall survival in medulloblastoma patients (P = 0.027; hazard ratio = 0.267). Our study provides the first demonstration that miR-495 directly interacts with the Gfi1 3’UTR to regulate Gfi1 at a post-transcriptional level and that the expression level of miR-495 is inversely correlated with the Gfi1 protein level in medulloblastoma specimens. CONCLUSION: Our results suggest that miR-495 may be a prognostic predictor in medulloblastoma and that Gfi1 is a potential functional target of miR-495.
BACKGROUND: Alterations in the expression level of miR-495 were recently observed in various tumours. Medulloblastoma is the most common malignant brain tumour in children. However, the clinical significance of miR-495 in medulloblastomas remains unclear. METHODS: The expression levels of miR-495 was examined in 62 archival formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens using TaqMan Real-time Quantitative PCR arrays. Immunohistochemistry was used to determine the expression of Gfi1 in medulloblastoma tissues, and a luciferase reporter assay was carried out to confirm whether Gfi1 is a direct target of miR-495. RESULTS:MiR-495 expression is repressed in medulloblastoma samples compared with normal cerebellum tissues. Furthermore, patients with a low level of miR- 495 showed significantly poorer survival, as determined by the log-rank test (P = 0.033). The multivariate analysis results showed that the miR-495 expression levels were an independent predictor of overall survival in medulloblastomapatients (P = 0.027; hazard ratio = 0.267). Our study provides the first demonstration that miR-495 directly interacts with the Gfi1 3’UTR to regulate Gfi1 at a post-transcriptional level and that the expression level of miR-495 is inversely correlated with the Gfi1 protein level in medulloblastoma specimens. CONCLUSION: Our results suggest that miR-495 may be a prognostic predictor in medulloblastoma and that Gfi1 is a potential functional target of miR-495.
Authors: Xin Wang; Borja L Holgado; Vijay Ramaswamy; Stephen Mack; Kory Zayne; Marc Remke; Xiaochong Wu; Livia Garzia; Craig Daniels; Anna M Kenney; Michael D Taylor Journal: Neuro Oncol Date: 2018-02-19 Impact factor: 12.300