Sang Liang, Sun Liping, Wang Ang, Zhang Han, Yuan Yuan
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China.
Department of Ultrasound, The First Hospital of China Medical University, Shenyang, China.
Front Genet. 2020 Nov 4;11:561566. doi: 10.3389/fgene.2020.561566. eCollection 2020.
Although N6-methyladenosine (m6A) mRNA methylation is known to be closely related to tumor events, its role in carcinogenesis and the development of gastric cancer (GC) is not yet clear. The aim of this study was to identify common m6A features and novel aberrant expression of m6A modified genes in GC and to further explore their potential impact on risk and prognosis. Three paired GC and paracancerous (PCa) tissues were collected to perform an m6A sequencing by MeRIP-seq and microarray assays. The expression profile of m6A and mRNA were determined. Gene function note and enrichment analysis were performed, and protein-protein interaction networks of differentially m6A methylated genes (DMGs) were generated using the DAVID and STRING databases, respectively. Validation of the m6A related differentially expressed genes by matching TCGA and GTEx data and human tissues. Clinical and pathological correlation and survival analysis were performed by TCGA data. The m6A motif sequence GGACAR ( = U or A) C was the consensus in both GC and PCa tissues. m6A peaks were significantly related to different coordinates, however, for most samples, the end of the coding sequence (CDS) was more prominent than the start of CDS. The genes with higher levels of m6A in their mRNAs were mainly enriched in transcriptional misregulation in carcinogenesis pathways, whereas the genes with decreased methylation mainly regulated digestion and absorption of protein. There are genes with differential m6A modifications in GC and paired PCa tissues, and these genes are mainly enriched in transcriptional misregulation and digestion/absorption pathways. m6A-GC with the down- and up-regulated genes may play an important role in gastric carcinogenesis, which can affect the risk and prognosis in GC.
虽然已知N6-甲基腺苷（m6A）mRNA甲基化与肿瘤事件密切相关，但其在胃癌（GC）发生和发展中的作用尚不清楚。本研究的目的是确定GC中m6A的常见特征和m6A修饰基因的新型异常表达，并进一步探讨它们对风险和预后的潜在影响。收集三对GC和癌旁（PCa）组织，通过MeRIP-seq和微阵列分析进行m6A测序。测定m6A和mRNA的表达谱。进行基因功能注释和富集分析，并分别使用DAVID和STRING数据库生成差异m6A甲基化基因（DMG）的蛋白质-蛋白质相互作用网络。通过匹配TCGA和GTEx数据以及人体组织对m6A相关差异表达基因进行验证。利用TCGA数据进行临床和病理相关性及生存分析。m6A基序序列GGACAR（=U或A）C是GC和PCa组织中的共有序列。m6A峰与不同坐标显著相关，然而，对于大多数样本，编码序列（CDS）的末端比CDS的起始端更突出。mRNA中m6A水平较高的基因主要富集在致癌途径中的转录失调，而甲基化降低的基因主要调节蛋白质的消化和吸收。GC和配对的PCa组织中存在具有差异m6A修饰的基因，这些基因主要富集在转录失调和消化/吸收途径中。m6A修饰下调和上调的基因可能在胃癌发生中起重要作用，这可能影响GC的风险和预后。
