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

Guo Hao Huang, Lei Du, Ningning Li, Ying Zhang, Yan Xiang, Jun Hai Tang, Shuli Xia, Eric Erquan Zhang, Sheng Qing Lv

Research output: Contribution to journalArticle

Abstract

Gliomas with isocitrate dehydrogenases gene mutations (IDHMT) were found to be less aggressive than their wildtype (IDHWT) counterparts. However, the mechanism remains unclear. The current study aims to investigate the role of silenced oncogenic microRNAs in IDHMT gliomas, which were largely ignored and may contribute to the less aggressive behavior of IDHMT gliomas. Microarrays, bioinformatics analysis of the data from TCGA and qPCR analysis of samples from our experimental cohort (LGG: IDHWT = 10, IDHMT = 31; GBM: IDHWT = 34, IDHMT = 9) were performed. The results show that miR-155 was consistently down-regulated in IDHMT gliomas. Establishment of IDH1R132H overexpressing glioma cell line and bisulfite sequencing PCR suggested that miR-155 down-regulation was associated with IDH1R132H 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 IDHMT gliomas by targeting MMP14.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalCancer Letters
Volume432
DOIs
Publication statusPublished - Sep 28 2018

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Keywords

  • Glioma
  • IDH mutation
  • Methylation
  • Migration and invasion
  • miR-155

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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