M5C RNA Methylation Primarily Affects the ErbB and PI3K-Akt Signaling Pathways in Gastrointestinal Cancer.

Shixin Xiang,Yuan Zheng,Huijiao Ji,Xu Wu,Qinglian Wen,Jing Shen,Zhangang Xiao,Yongshun Ma,Yueshui Zhao,Xiang Li,Fukuan Du,Mingxing Li,Xiao Yang,Jing Li,Parham Jabbarzadeh Kaboli

doi:10.3389/fmolb.2020.599340

Abstract

5-Methylcytosine (m5C) 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 m5C is modulated by regulatory proteins, including methyltransferases (writers) and special binding proteins (readers). This study aims at comprehensive study of the m5C RNA methylation-related genes and the main pathways under m5C RNA methylation in gastrointestinal (GI) cancer. Our result showed that the expression of m5C 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 m5C regulators was significantly associated with lower patient survival rate. In addition, the expression level of m5C-related genes is significantly different at various pathological stages. Finally, we have found through bioinformatics analysis that m5C regulatory proteins are closely related to the ErbB/PI3K–Akt signaling pathway and GSK3B was an important target for m5C regulators. Besides, the compound termed streptozotocin may be a key candidate drug targeting on GSK3B for molecular targeted therapy in GI cancer.

Highlights

Gastrointestinal (GI) cancer is one of the leading causes of death worldwide
The results indicated that writers and reader were mostly up-regulated in GI cancer (Figure 2B)
Among 34 pathways, we found some major pathways affected by m5C regulators: ErbB, PI3K–Akt, HIF-1, and mTOR signaling pathways

Summary

Introduction

Gastrointestinal (GI) cancer is one of the leading causes of death worldwide. It refers to cancers of the upper and lower digestive tracts and mainly includes colorectal adenocarcinoma (CRC), gastric cancer (GC), pancreatic cancer (PC), hepatocellular carcinoma (HCC), and esophageal cancer (EC) (Toomey et al, 2013). 4.1 million people are diagnosed with GI cancer each year. Epigenetic changes are common events in both initiation and progression of GI cancer (Vedeld et al, 2018). There are many ways to treat GI cancer. Most of the treatment outcomes are still poor (Bilgin et al, 2017)

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Results