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5-Methylcytosine (m 5 C) is a kind of methylation modification that occurs in both DNA and RNA and is present in the highly abundant tRNA and rRNA. It has an important impact on various human diseases including cancer. The function of m 5 C is modulated by regulatory proteins, including methyltransferases (writers) and special binding proteins (readers). This study aims at comprehensive study of the m 5 C RNA methylation-related genes and the main pathways under m 5 C RNA methylation in gastrointestinal (GI) cancer. Our result showed that the expression of m 5 C writers and reader was mostly up-regulated in GI cancer. The  NSUN2  gene has the highest proportion of mutations found in GI cancer. Importantly, in liver cancer, higher expression of almost all m 5 C regulators was significantly associated with lower patient survival rate. In addition, the expression level of m 5 C-related genes is significantly different at various pathological stages. Finally, we have found through bioinformatics analysis that m 5 C regulatory proteins are closely related to the ErbB/PI3K–Akt signaling pathway and  GSK3B  was an important target for m 5 C regulators. Besides, the compound termed streptozotocin may be a key candidate drug targeting on GSK3B for molecular targeted therapy in GI cancer.

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer