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在大鼠的巴雷特食道中对全转录组N6-甲基氨酸甲基组进行了全面的分析

Ke Zou¹, Hui Dong², Mengmeng Li²

¹Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250013, China; Jinan Central Hospital, Shandong University, No. 105, Jiefang Road, Jinan, Shandong 250013, China; Jinan Digestive Diseases Clinical Research Center, No. 105, Jiefang Road, Jinan, Shandong 250013, China; Jinan Key Translational Research Laboratory in Gastroenterology, No. 105, Jiefang Road, Jinan, Shandong 250013, China; Shandong University, No. 44, Wenhua west Road, Jinan, Shandong 250102, China.

|July 16, 2023

概括

这项研究绘制了巴雷特食道 (BE) 中的N6-甲基氨酸 (m6A) RNA修饰模式,确定了参与其发展为食道腺癌 (EAC) 的关键基因和潜在的治疗点.

科学领域:

表观遗传学和RNA生物学
胃肠道学和瘤学

背景情况:

N6-甲基氨酸 (m6A) 是最丰富的RNA修饰,在各种疾病过程中发挥关键作用.
巴雷特食道 (BE) 是食道腺癌 (EAC) 的前体,需要对其分子基础有更深入的了解.

研究的目的:

为了全面地绘制巴雷特食道 (BE) 中的mRNA m6A修饰景观.
为了确定关键的基因和潜在的治疗策略,为BE和食道腺癌 (EAC).

主要方法:

甲基化RNA免疫沉降测序 (MeRIP-seq) 和RNA测序 (RNA-seq) 用于比较BE和正常对照 (NC) 组织之间的m6A甲基化和基因表达特征.
生物信息学分析,包括途径丰富和蛋白质-蛋白质相互作用 (PPI) 网络构建,用于分析m6A修饰模式并识别重要的基因.

主要成果:

MeRIP-seq在BE组织中发现了11,026个独特的m6A峰值,而在NC组织中为8564,主要是用GGACU图案丰富的CDS.
功能性丰富分析显示,信号传递和MAPK信号传递等途径中,高甲基和低甲基基因的丰富程度显著.
确定了18个枢纽基因,其中几个 (例如ACTA1,CDC20,KIF20a) 在EAC表现过度,影响患者的存活率,这表明它们在疾病进展中的作用.

结论:

这项研究提供了首个全面的m6A甲基化在BE的全转录组图,突出了其在氧化应激和疾病发病过程中的潜在作用.
鉴定到的m6A修饰基因和通路为驱动BE和EAC的分子机制提供了新的见解,为向治疗铺平了道路.

关键词:

巴雷特的食道.消化道的腺癌瘤.这就是MeRIP-seqq.在RNA-seqqq.m6A 一个很好的.

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