MiR-449a is a potential epigenetic biomarker for WNT subtype of medulloblastoma

Abstract

Objective: To identify the candidate epigenetic biomarkers of Wnt subtype of medulloblastoma(MB). Methods: MicroRNAs(miRNAs) expression array was used to detect the expression of miRNAs in MB cell lines with or without treatment by demethylation reagent. Nanostring gene expression array was used to detect the expression level of mRNA in 45 samples of primary MB. Molecular subtyping was performed based on the NanoString data. The status of methylation was confirmed by methylation specific PCR. The expression of candidate miRNA was confirmed by real-time PCR. Results: All 45 MBs except one were classified into the four molecular groups: 4 in WNT group, 8 in SHH group, 16 were in Group3 and 16 in Group4. Methylation specific PCR (MSP) assay confirmed miR-449a was silenced due to aberrant DNA methylation in MB cell lines.WNT subtype of MBs showed relatively higher expression of miR-449a comparing with other subgroups. Conclusion: MiR-449a, a candidate tumor suppressor gene regulated by hypermethylation, is a novel potential epigenetic marker for WNT subtype of MBs.