# The Emerging Roles of RNA Modifications in Glioblastoma
## 1 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]. It accounts for about 50% of all brain neoplasms and has a median survival time of approximately 14.6 months [2]. The annual worldwide occurrence of this disease is about five cases per 100,000 people [3]. Currently, the origin of GBM is mainly the poorly differentiated glial cell, which is characterized with nuclear atypia, cellular polymorphism and high mitotic activity [4]. Since GBM is very aggressive and invasive, it is difficult to remove all the neoplastic lesions from the brain by using surgical resection. Subsequently, the patients typically receive 30-week radiotherapy and an adjuvant chemotherapeutic alkylating drug,temozolomide (TMZ) [3]. However, since GBM is highly heterogeneous, the effect is limited and no remarkable progression has been achieved yet. Therefore, it is urgent to develop new therapeutic strategies to treat GBM; however, the natural characteristics of GBM remain not fully understood.  
To know how GBM initiates and develops, the molecular characteristics of GBM should be accurately determined. Actually, 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. Particularly, covalent modifications in DNA and histones, also known as that main concept of epigenetics, play important roles in regulating cell fate determination, cell proliferation, cellular metabolism and even many pathological processes [10; 11; 12; 13; 14]. Recently, the RNA world has become a new area to be explored for cancer therapy. Both coding and non-coding mRNAs have many diverse functions in addition to their traditional functions. Studies on RNA processing, editing, splicing, polyadenylation, post-transcription of RNA and RNA-binding proteins are developing very fast [15; 16; 17; 18], leading to a new area called the epi-transcriptome. Covalent modifications in RNA and their connections with cancers are also an area of concentrated activity in cancer biology research [19].  
Recently, RNA modifications, as known as RNA epigenetics, were found to be present in almost all the cellular RNAs in archaeobacteria, bacteria, prototists, plants, fungi, animals and viruses. Even in mitochondria, there are also some chemical modifications in mitochondrial DNA-encoded RNAs [20]. More than 170 kinds of covalent modifications have been found in RNAs at present [21; 22], however, the functional implications of most of them remain unravelled. These kinds of biological modifications exercise important regulation functions during both normal and pathological bioprocesses and tissue development. Importantly, RNA modifications, especially N\({}^{6}\)-methyladenosine (m\({}^{6}\)A) modification, are shown to be essential for tumor development [22; 23; 24; 25].  
In this review, we summarize the most recent advances in RNA modifications, especially the functions of m\({}^{6}\)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.