Lin Yu, Zhao Zhifang, Nie Wenqiang, Huang Manting, Cai Jiazhong, Wang Yadong, Wang Hesong, Huang Yongmei, Bai Yang
Department Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nan Fang Hospital, Southern Medical University, Guangzhou, China.
Department of Gastroenterology, Baiyun Branch, Nan Fang Hospital, Southern Medical University, Guangzhou, China.
Front Genet. 2023 Apr 24;14:1121063. doi: 10.3389/fgene.2023.1121063. eCollection 2023.
Colorectal cancer (CRC) is a harmful cancer with high morbidity and poor prognosis. There is growing evidence that RNA methylation is closely related to the occurrence of cancer and its malignant biological behavior. N6-methyladenosine (mA) methylation is the most common RNA modification in eukaryotes, and its multiple regulatory mechanisms in CRC have been elucidated from multiple perspectives. At the same time, the role of 5-methylcytosine (m5C), another important and widely distributed methylation modification, in CRC is far from being elucidated. In this study, we used RNA immunoprecipitation sequencing combined with bioinformatics methods to identify the m5C peaks on messenger RNA (mRNA) in HCT15 cells and sh-NSUN2 HCT15 cells, understand which transcripts are modified by m5C, and characterize the distribution of m5C modifications. In addition, we performed further bioinformatics analysis of the detected data to initially clarify the potential function of these m5C-modified transcripts. We found significant differences in the distribution of m5C between HCT15 cells and sh-NSUN2 HCT15 cells, suggesting that m5C is likely to play a key role in the occurrence and development of CRC. Furthermore, Gene Ontology (GO) enrichment analysis showed that genes altered by m5C were mainly enriched in phylogeny, synaptic membrane, and transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analysis showed that the genes altered by m5C are enriched in ECM receptor interaction pathway, the circadian pathway, and the cAMP signaling pathway. Here, our study preliminarily revealed the different distribution patterns of m5C between HCT15 cell and sh-NSUN2 HCT15 cell. Our results open a new window to understand the role of m5C RNA methylation of mRNA in the development of CRC.
结直肠癌（CRC）是一种危害性大、发病率高且预后不良的癌症。越来越多的证据表明，RNA甲基化与癌症的发生及其恶性生物学行为密切相关。N6-甲基腺苷（m⁶A）甲基化是真核生物中最常见的RNA修饰，其在结直肠癌中的多种调控机制已从多个角度得到阐明。与此同时，另一种重要且广泛分布的甲基化修饰——5-甲基胞嘧啶（m⁵C）在结直肠癌中的作用远未阐明。在本研究中，我们使用RNA免疫沉淀测序结合生物信息学方法，鉴定HCT15细胞和sh-NSUN2 HCT15细胞中信使核糖核酸（mRNA）上的m⁵C峰，了解哪些转录本被m⁵C修饰，并表征m⁵C修饰的分布情况。此外，我们对检测到的数据进行了进一步的生物信息学分析，以初步阐明这些m⁵C修饰转录本的潜在功能。我们发现HCT15细胞和sh-NSUN2 HCT15细胞之间m⁵C的分布存在显著差异，这表明m⁵C可能在结直肠癌的发生和发展中起关键作用。此外，基因本体论（GO）富集分析表明，被m⁵C改变的基因主要富集在系统发育、突触膜和转录因子结合方面。京都基因与基因组百科全书（KEGG）通路分析表明，被m⁵C改变的基因富集在细胞外基质受体相互作用通路、昼夜节律通路和环磷酸腺苷（cAMP）信号通路中。在此，我们的研究初步揭示了HCT15细胞和sh-NSUN2 HCT15细胞之间m⁵C的不同分布模式。我们的结果为了解mRNA的m⁵C RNA甲基化在结直肠癌发生发展中的作用打开了一扇新窗口。
