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Published on: October 4, 2019
MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma
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.
Insights
MicroRNA-495 (miR-495) is repressed in pediatric medulloblastoma, and low levels predict poorer survival. MiR-495 directly targets Gfi1, suggesting its potential as a prognostic biomarker for this brain tumor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-495 (miR-495) expression is altered in various cancers.
- Medulloblastoma is the most common pediatric malignant brain tumor.
- The clinical role of miR-495 in medulloblastoma is not well understood.
Purpose of the Study:
- To investigate the clinical significance of miR-495 in medulloblastoma.
- To determine if miR-495 functions as a prognostic predictor.
- To identify potential targets of miR-495 in medulloblastoma.
Main Methods:
- Quantitative real-time PCR (TaqMan arrays) to measure miR-495 expression in 62 medulloblastoma specimens.
- Immunohistochemistry to assess Gfi1 protein levels.
- Luciferase reporter assay to validate Gfi1 as a direct miR-495 target.
Main Results:
- MiR-495 expression was significantly lower in medulloblastoma tissues compared to normal cerebellum.
- Low miR-495 levels correlated with significantly poorer patient survival (P = 0.033).
- MiR-495 expression is an independent predictor of overall survival (P = 0.027) and directly targets Gfi1 at the post-transcriptional level, showing an inverse correlation with Gfi1 protein levels.
Conclusions:
- MiR-495 may serve as a valuable prognostic biomarker for medulloblastoma.
- Gfi1 is identified as a potential functional target regulated by miR-495.
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