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

被引:22
|
作者
Xiang, Shixin [1 ,2 ]
Ma, Yongshun [1 ,2 ]
Shen, Jing [1 ,2 ]
Zhao, Yueshui [1 ,2 ]
Wu, Xu [1 ,2 ]
Li, Mingxing [1 ,2 ]
Yang, Xiao [1 ]
Kaboli, Parham Jabbarzadeh [1 ,2 ]
Du, Fukuan [1 ,2 ]
Ji, Huijiao [1 ,2 ]
Zheng, Yuan [3 ]
Li, Xiang [1 ]
Li, Jing [4 ]
Wen, Qinglian [5 ]
Xiao, Zhangang [1 ,2 ]
机构
[1] Southwest Med Univ, Sch Pharm, Dept Pharmacol, Mol Pharmacol Lab, Luzhou, Peoples R China
[2] South Sichuan Inst Translat Med, Luzhou, Peoples R China
[3] Neijiang Hlth & Hlth Vocat Coll, Neijiang, Peoples R China
[4] Southwest Med Univ, Dept Hematol & Oncol, Hosp TCM, Luzhou, Peoples R China
[5] Southwest Med Univ, Affiliated Hosp, Dept Oncol, Luzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
m(5)C; RNA methylation; ErbB; PI3K– Akt; gastrointestinal cancer; survival; DRUG TARGET IDENTIFICATION; MESSENGER-RNA; GENE-EXPRESSION; SATELLITE REGIONS; CONNECTIVITY MAP; DNA METHYLATION; CPG ISLANDS; WEB SERVER; NSUN2; METHYLTRANSFERASE;
D O I
10.3389/fmolb.2020.599340
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:17
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