MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma.

Abstract

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.

• Authors: Ce Wang, Zhiyuan Yun, Tianshu Zhao, Xian Liu, Xueling Ma
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 36 Issue 4 Pg. 1430-9 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26160036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• GFI1 protein, human
• MIRN495 microRNA, human
• MicroRNAs
• Transcription Factors

Topics

• Adolescent
• Adult
• Base Sequence
• Biomarkers, Tumor (analysis, genetics)
• Cell Line, Tumor
• Cerebellar Neoplasms (diagnosis, genetics, pathology)
• Cerebellum (metabolism, pathology)
• Child
• Child, Preschool
• DNA-Binding Proteins (analysis, genetics)
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Infant
• Male
• Medulloblastoma (diagnosis, genetics, pathology)
• MicroRNAs (analysis, genetics)
• Middle Aged
• Prognosis
• Real-Time Polymerase Chain Reaction
• Survival Analysis
• Transcription Factors (analysis, genetics)
• Young Adult