Abstract
N6-methyladenosine (m6A) is the most common form of mRNA modification, and is dynamically regulated by the m6A RNA methylation regulators. However, little is known about m6A in gastric cancer. The aim of this work is to investigate the effects of m6A RNA methylation regulators in gastric cancer. Here, we found that most of the 13 main m6A RNA methylation regulators are higher expressed in 375 patients with gastric cancer. We identified two subgroups of gastric cancer (cluster1 and 2) by applying consensus clustering to m6A RNA methylation regulators. Compared with the cluster1 subgroup, the cluster2 subgroup correlates with a poorer prognosis, and most of the 13 main m6A RNA methylation regulators are higher expressed in cluster2. Moreover, the cancer-specific pathways are also significantly enriched in the cluster2 subgroup. This finding indicates that m6A RNA methylation regulators are closely associated with gastric cancer. Based on this finding, we derived a risk signature, using 3 m6A RNA methylation regulators (FTO, RBM15, ALKBH5), that is not only an independent prognostic marker but can also predict the clinicopathological features of gastric cancer. Moreover, FTO is higher expressed in high risk scores subtype in gastric cancer. Thus, this first finding provide us clues to understand epigenetic modification of RNA in gastric cancer.
Highlights
N6-methyladenosine (m6A) is a methylation modification that can occur on RNA adenine (A) [1]
Compared with normal gastric tissue, gastric cancer patients generally contain a higher proportion of METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, and FTO (Figures 1A,B)
We systematically investigated the relationships between each individual m6A RNA methylation regulator and the pathological features of gastric cancer, including age, gender, grades, stage status, T status, M status, and N status, and found there is relationship between m6A
Summary
N6-methyladenosine (m6A) is a methylation modification that can occur on RNA adenine (A) [1]. Instead, it was aggregated in the stop codon, 3′ untranslated region (3′UTR), and internal exons [9,10,11], and more were found in the precursor mRNA [12]. Through the study of m6A related proteins, it is found that m6A methylation is a dynamic reversible process [16], which is composed of methyltransferase complex (writers), demethylase (erasers), and function manager (readers) [17]. Relying on the role of “Erasers,” the process of m6A modification becomes dynamic and reversible, thereby functioning to regulate the expression of various genes [14]
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