Methylation-mediated miR-155-FAM133A axis contributes to the attenuated invasion and migration of IDH mutant gliomas

Abstract

Gliomas with isocitrate dehydrogenases gene mutations (IDH^MT) were found to be less aggressive than their wildtype (IDH^WT) counterparts. However, the mechanism remains unclear. The current study aims to investigate the role of silenced oncogenic microRNAs in IDH^MT gliomas, which were largely ignored and may contribute to the less aggressive behavior of IDH^MT gliomas. Microarrays, bioinformatics analysis of the data from TCGA and qPCR analysis of samples from our experimental cohort (LGG: IDH^WT = 10, IDH^MT = 31; GBM: IDH^WT = 34, IDH^MT = 9) were performed. The results show that miR-155 was consistently down-regulated in IDH^MT gliomas. Establishment of IDH1^R132H overexpressing glioma cell line and bisulfite sequencing PCR suggested that miR-155 down-regulation was associated with IDH1^R132H mutation induced promoter CpG islands methylation. The cancer testis antigen FAM133A is a direct downstream target of miR-155 and is a negative regulator of glioma invasion and migration possibly by regulating matrix metallopeptidase 14 (MMP14). Together, we found that methylation-regulated miR-155-FAM133A axis may contribute to the attenuated invasion and migration of IDH^MT gliomas by targeting MMP14.

Keywords: Glioma; IDH mutation; Methylation; Migration and invasion; miR-155.