The Emerging Roles of RNA Modifications in Glioblastoma.

Zhen Dong,Hongjuan Cui

doi:10.3390/cancers12030736

Abstract

Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

Highlights

Glioblastoma (GBM), a World Health Organization (WHO) grade IV glioma, is the most prevalent, malignant and lethal intrinsic tumor in the central nervous system [1]
ribonucleic acid (RNA) m6 A modification is the most prevalent and abundant modifications that occur in the messenger RNAs (mRNAs), ribosomal RNAs (rRNAs) and small nuclear RNAs [35]. m6 A modification of mRNA usually occurs in nuclear speckles where the methyltransferases and demethylases are concentrated [29] and are enriched in single nucleotide polymorphisms (SNPs) [36]
2 (MMP-2), and the proto-oncogene RON [74,75]. These results indicate that heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) and hnRNPA2B1 are possible m6 A readers that contribute to GBM pathogenesis

Summary

Introduction

Glioblastoma (GBM), a World Health Organization (WHO) grade IV glioma, is the most prevalent, malignant and lethal intrinsic tumor in the central nervous system [1]. Many genetic, epigenetic, metabolic and immunologic profiles in GBM have been described in recent years [5,6,7,8,9] These landscapes of GBM have greatly expanded our knowledge about GBM, thereby providing clues for the treatment of this disease. The RNA world has become a new area to be explored for cancer therapy. We summarize the most recent advances in RNA modifications, especially the functions of m6 A writers, erasers and readers, and their molecular mechanisms of action in GBM, so as to provide some clues for the development of new strategies for GBM treatment

RNA Modifications

13. Others

RNA Modifications in GBM

RNA m6 A Modification in GBM

RNA m6 A Writers in GBM

RNA m6 A Erasers in GBM

RNA m6 A Readers in GBM

RNA m6 Am Modification in GBM

RNA m5 C Modification in GBM

RNA hm5 C Modification in GBM

RNA m1 A Modification in GBM

RNA A-To-I Modification in GBM