Format

Send to

Choose Destination
Cancer Lett. 2018 Sep 28;432:93-102. doi: 10.1016/j.canlet.2018.06.007. Epub 2018 Jun 6.

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

Author information

1
Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
2
The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
3
Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, WC1N 3BG, UK.
4
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
5
National Institute of Biological Sciences, Beijing, 102206, China.
6
Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. Electronic address: lvsq0518@hotmail.com.

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.

KEYWORDS:

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

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center