Lin Zhen-Liang, Yu Pan-Pan, Ye Bei-Lei
Department of Surgery, The Affiliated Cangnan Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, China.
Front Genet. 2025 Aug 14;16:1622957. doi: 10.3389/fgene.2025.1622957. eCollection 2025.
RNA N6-methyladenosine (m6A) methylation is a major epigenetic modification that plays a critical role in regulating gene expression in tumors. Although the regulation of individual genes by m6A methylation has been extensively studied, a systematic quantification of transcriptome-wide associations between RNA methylation and gene expression remains limited. In this study, we analyzed publicly available MeRIP-seq and RNA-seq datasets of paired colorectal cancer (CRC) and adjacent normal tissues from four patients, proposing a statistical model to quantify the cis-regulation between m6A methylation and gene expression in CRC. The results indicated that (1) A total of 46,500 and 31,715 unique m6A peaks were identified in CRC and normal control (NC) tissues, respectively. Compared with NC tissues, 538 genes were upregulated and 3,944 were downregulated in CRC tissues (padj <0.05 and |logFC| > 1). (2) Approximately 66.01% of m6A peaks in CRC are located within genes and 28.78% in promoters, compared to 65.00% and 28.38%, respectively, in NC tissues. CRC tissues exhibited higher methylation levels in exons and 3'UTRs, while NC tissues showed increased methylation in introns. (3) 451 genes exhibited significant cis-regulation between RNA methylation and gene expression. Among these, 371 genes were positively correlated, indicating a promotive effect on gene expression, while 80 genes showed negative correlation. Moreover, 34 genes showing strong correlations ( ≥ 0.9) were identified, including 16 genes previously reported to be associated with CRC. This study provides a transcriptome-wide strategy for quantifying the association between RNA methylation and gene expression in CRC, offering new insights into the potential regulatory roles of RNA methylation in tumor biology.
RNA N6-甲基腺苷（m6A）甲基化是一种主要的表观遗传修饰，在调节肿瘤基因表达中起关键作用。尽管m6A甲基化对单个基因的调控已得到广泛研究，但对RNA甲基化与基因表达之间全转录组关联的系统定量研究仍然有限。在本研究中，我们分析了来自4名患者的配对结直肠癌（CRC）和癌旁正常组织的公开可用MeRIP-seq和RNA-seq数据集，提出了一个统计模型来定量CRC中m6A甲基化与基因表达之间的顺式调控。结果表明：（1）在CRC组织和正常对照（NC）组织中分别鉴定出46,500个和31,715个独特的m6A峰。与NC组织相比，CRC组织中有538个基因上调，3,944个基因下调（padj<0.05且|logFC|>1）。（2）CRC中约66.01%的m6A峰位于基因内，28.78%位于启动子区域，而NC组织中分别为65.00%和28.38%。CRC组织在外显子和3'UTR中表现出较高的甲基化水平，而NC组织在内含子中甲基化增加。（3）451个基因在RNA甲基化与基因表达之间表现出显著的顺式调控。其中，371个基因呈正相关，表明对基因表达有促进作用，而80个基因呈负相关。此外，鉴定出34个强相关基因（≥0.9），包括16个先前报道与CRC相关的基因。本研究提供了一种全转录组策略，用于定量CRC中RNA甲基化与基因表达之间的关联，为RNA甲基化在肿瘤生物学中的潜在调控作用提供了新的见解。
