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m⁶A RNA甲基化主要影响胃肠道癌中的表皮生长因子受体（ErbB）和磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路。

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

作者信息

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

机构信息

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.

South Sichuan Institute of Translational Medicine, Luzhou, China.

出版信息

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

DOI:10.3389/fmolb.2020.599340
PMID:33365328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7750483/
Abstract

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

摘要

5-甲基胞嘧啶（mC）是一种发生于DNA和RNA的甲基化修饰，存在于高度丰富的转运RNA（tRNA）和核糖体RNA（rRNA）中。它对包括癌症在内的多种人类疾病具有重要影响。mC的功能由调控蛋白调节，包括甲基转移酶（写入器）和特殊结合蛋白（读取器）。本研究旨在全面研究胃肠道（GI）癌中与mC RNA甲基化相关的基因以及mC RNA甲基化作用下的主要信号通路。我们的结果显示，mC写入器和读取器的表达在GI癌中大多上调。该基因在GI癌中发现的突变比例最高。重要的是，在肝癌中，几乎所有mC调节因子的高表达都与患者较低的生存率显著相关。此外，mC相关基因的表达水平在不同病理阶段存在显著差异。最后，我们通过生物信息学分析发现，mC调节蛋白与表皮生长因子受体（ErbB）/磷脂酰肌醇-3激酶（PI3K）-蛋白激酶B（Akt）信号通路密切相关，并且是mC调节因子的一个重要靶点。此外，名为链脲佐菌素的化合物可能是针对糖原合成酶激酶3β（GSK3B）进行GI癌分子靶向治疗的关键候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2047/7750483/e7a1f9b860ba/fmolb-07-599340-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2047/7750483/fd4d241c0456/fmolb-07-599340-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2047/7750483/e7a1f9b860ba/fmolb-07-599340-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2047/7750483/e7a1f9b860ba/fmolb-07-599340-g008.jpg

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