Malignant Evaluation and Clinical Prognostic Values of m6A RNA Methylation Regulators in Glioblastoma

Abstract

N6-methyladenosine (m6A) RNA methylation, the most common form of mRNA modification and regulated by the m6A RNA methylation regulators ("writers," "erasers," and "readers"), has been reported to be associated with the progression of the malignant tumor. However, its role in glioblastoma (GBM) has been poorly known. This study aimed to identify the expression, potential functions, and prognostic values of m6A RNA methylation regulators in GBM. Here, we revealed that the 13 central m6A RNA methylation regulators were firmly related to the clinical and molecular phenotype of GBM. Taking advantage of consensus cluster analysis, we obtained two categories of GBM samples and found malignancy-related processes of m6A methylation regulators and compounds that specifically targeted the malignant processes. Besides, we also obtained a list of genes with poor prognosis in GBM. Finally, we derived a risk-gene signature with three selected m6A RNA methylation regulators, which allowed us to extend the in-depth study and dichotomized the OS of patients with GBM into high-and low-risk subgroups. Notably, this risk-gene signature could be used as independent prognostic markers and accurate clinicopathological parameter predictors. In conclusion, m6A RNA methylation regulators are a type of vital participant in the malignant progression of GBM, with a critical potential in the prognostic stratification and treatment strategies of GBM.

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

“…Previous studies have reported the bioinformatics analysis of total 13 m 6 A-related genes in gastric cancer ( 17 ), bladder cancer ( 18 ), and other cancers ( 19 , 20 ). In our study, a total of 19 m 6 A RNA methylation regulators were included for systematically analysis based on the recent the m 6 A review ( 9 ).…”

Identification of Prognostic Model and Biomarkers for Cancer Stem Cell Characteristics in Glioblastoma by Network Analysis of Multi-Omics Data and Stemness Indices

“…MTT was applied to test the viability of GSCs. It is worth noting that YTHDF2, as a reader of RNA m6A methylation, has been validated to be related to TMZ resistance in GSCs (Du et al, 2020). We found that TMZ and shYTHDF2 could synergistically inhibit the viability of GSCs (Figure 8H).…”

m6A RNA methylation regulators could contribute to the occurrence of chronic obstructive pulmonary disease

“…Certain types of RNA modifications in eukaryotic mRNA, such as 5‐methylcytosine (m5C), N1‐methyladenosine (m1A) and N6‐methyladenosine (m6A), have widely discovered, 4 among which m6A RNA methylation was first discovered in the 1970s 5 . The m6A RNA methylation, the most common form of dynamic and reversible mRNA modification, is regulated by m6A RNA methylation regulators, containing methyltransferases (‘writers’) that install m6A mark, demethylases (‘erasers’) that reverse m6A mark, and m6A binding proteins (‘readers’) that decode m6A modification to mediate the fate of modified transcripts 6–8 . Currently, at least ten proteins have been found in the m6A ‘writers’ complex, containing WT1‐associated protein (WTAP), methyltransferase like 3/4/14 (METTL3/4/14), Cbl Proto‐Oncogene Like 1 (CBLL1), RNA‐binding motif protein15/15B (RBM15/15B), Vir like m6A methyltransferase associated VIRMA (VIRMA/KIAA1429), Zinc Finger Protein 217 (ZNF217) and zinc finger CCCH domain‐containing protein 13 (ZC3H13) 3,4,6,8,9 .…”

“…9 Twelve proteins have been identified in the m6A 'readers', including YT521-B homology (YTH) domain-containing proteins (YTHDC1/2), eukaryotic translation initiation factor 3 subunit A/B (EIF3A/B), YTH N6-methyladenosine RNA-binding proteins (YTHDF1/2/3), insulin like growth factor 2 mRNA binding protein families (IGF2BP1/2/3) and heterogeneous nuclear ribonucleoprotein (HNRNP) protein families (HNRNPA2B1 and HNRNPC). 3,4,6,8,9 The m6A RNA methylation modulated by these regulators has been found to influence mRNA at different levels, containing structure, maturation, splicing, nuclear export, translation, localization, stability and decay, 3,4,[6][7][8][9] playing important roles in diverse physiological processes, including development, fertility, stemness, meiosis, carcinogenesis, circadian cycle, cell fate decision, cell differentiation, cell cycle regulation and circadian rhythm maintenance and human diseases. 6,8,10 Particularly, an increasing number of in vivo and in vitro experiments and bioinformatic researches showed that m6A RNA methylation regulators contribute to the occurrence, development and clinical prognosis of multiple various cancers, 4,[6][7][8][9][11][12][13][14] while the role of m6A RNA methylation regulators in COPD and their association with COPD genes are never reported.…”

“…Numerous studies have demonstrated that m6A RNA methylation regulators contribute to the occurrence, development and clinical prognosis of multiple various cancers,4,[6][7][8][9][11][12][13][14] due to its capacity of modulating RNA splicing, translocation, translation and stability. However, the understanding of m6A modification remains blank in COPD.…”