Format

Send to

Choose Destination
Aging (Albany NY). 2019 Feb 27;11(4):1204-1225. doi: 10.18632/aging.101829.

m6A RNA methylation regulators contribute to malignant progression and have clinical prognostic impact in gliomas.

Chai RC#1,2,3, Wu F#1,3, Wang QX#4,3, Zhang S4, Zhang KN1,3, Liu YQ1,3, Zhao Z1,3, Jiang T1,5,2,3, Wang YZ1,5,2,3, Kang CS4,3,6.

Author information

1
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100160, China.
2
China National Clinical Research Center for Neurological Diseases, Beijing, China.
3
Chinese Glioma Genome Atlas Network (CGGA).
4
Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital and Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China.
5
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100160, China.
6
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China.
#
Contributed equally

Abstract

N6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators ("writers", "erasers" and "readers"). Here, we demonstrate that most of the thirteen main m6A RNA methylation regulators are differentially expressed among gliomas stratified by different clinicopathological features in 904 gliomas. We identified two subgroups of gliomas (RM1/2) by applying consensus clustering to m6A RNA methylation regulators. Compared with the RM1 subgroup, the RM2 subgroup correlates with a poorer prognosis, higher WHO grade, and lower frequency of IDH mutation. Moreover, the hallmarks of epithelial-mesenchymal transition and TNFα signaling via NF-κB are also significantly enriched in the RM2 subgroup. This finding indicates that m6A RNA methylation regulators are closely associated with glioma malignancy. Based on this finding, we derived a risk signature, using seven m6A RNA methylation regulators, that is not only an independent prognostic marker but can also predict the clinicopathological features of gliomas. Moreover, m6A regulators are associated with the mesenchymal subtype and TMZ sensitivity in GBM. In conclusion, m6A RNA methylation regulators are crucial participants in the malignant progression of gliomas and are potentially useful for prognostic stratification and treatment strategy development.

KEYWORDS:

RNA modification; demethylases; epigenetics; methyltransferase; prognostic signature

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center