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

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

doi:10.3389/fmolb.2020.599340

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

Front Mol Biosci. 2020 Dec 7:7:599340. doi: 10.3389/fmolb.2020.599340. eCollection 2020.

Authors

Shixin Xiang^{1

2}, Yongshun Ma^{1

2}, Jing Shen^{1

2}, Yueshui Zhao^{1

2}, Xu Wu^{1

2}, Mingxing Li^{1

2}, Xiao Yang¹, Parham Jabbarzadeh Kaboli^{1

2}, Fukuan Du^{1

2}, Huijiao Ji^{1

2}, Yuan Zheng³, Xiang Li¹, Jing Li⁴, Qinglian Wen⁵, Zhangang Xiao^{1

2}

Affiliations

¹ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
² South Sichuan Institute of Translational Medicine, Luzhou, China.
³ Neijiang Health and Health Vocational College, Neijiang, China.
⁴ Department of Oncology and Hematology, Hospital (T.C.M.) Affiliated to Southwest Medical University, Luzhou, China.
⁵ Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, China.

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.

Keywords: ErbB; PI3K–Akt; RNA methylation; gastrointestinal cancer; m5C; survival.