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Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells
Frontiers in Oncology ( IF 4.7 ) Pub Date : 2022-09-28 , DOI: 10.3389/fonc.2022.939449
Xun Chen 1 , Liutao Chen 2, 3 , Yuquan Tang 1 , Yi He 1 , Kuangwu Pan 1 , Linyu Yuan 1 , Weihong Xie 1 , Shangwu Chen 2, 3 , Wei Zhao 1 , Dongsheng Yu 1
Affiliation  

As the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different downstream biological functions. mRNA m6A modification and its corresponding regulators play an important role in cancers, but its characteristics in the precancerous stage are still unclear. In this study, we used oral precancerous DOK cells as a model to explore the characteristics of transcriptome-wide m6A modification and major m6A regulator expression in the precancerous stage compared with normal oral epithelial cell HOEC and oral cancer cell SCC-9 through MeRIP-seq and RT-PCR. Compared with HOEC cells, we found 1180 hyper-methylated and 1606 hypo-methylated m6A peaks and 354 differentially expressed mRNAs with differential m6A peaks in DOK cells. Although the change of m6A modification in DOK cells was less than that in SCC-9 cells, mRNAs with differential m6A in both cell lines were enriched into many identical GO terms and KEGG pathways. Among the 20 known m6A regulatory genes, FTO, ALKBH5, METTL3 and VIRMA were upregulated or downregulated in DOK cells, and the expression levels of 10 genes such as METTL14/16, FTO and IGF2BP2/3 were significantly changed in SCC-9 cells. Our data suggest that precancerous cells showed, to some extent, changes of m6A modification. Identifying some key m6A targets and corresponding regulators in precancerous stage may provide potential intervention targets for the prevention of cancer development through epigenetic modification in the future.



中文翻译:

转录组范围的 m6A 甲基化组分析揭示了口腔癌前细胞与正常口腔上皮细胞相比 m6A 修饰的变化

作为最常见的转录后RNA修饰,m 6 A甲基化广泛调节RNA的结构和功能。m 6 A的动态和可逆修改由 m 6 A 写入器和擦除器协调。m 6 A 阅读蛋白识别 RNA 上的 m 6 A 修饰,介导不同的下游生物学功能。mRNA m 6 A 修饰及其相应的调节因子在癌症中发挥重要作用,但其在癌前阶段的特征仍不清楚。在本研究中,我们以口腔癌前 DOK 细胞为模型,探索全转录组 m 6 A 修饰和主要 m 6的特征。通过 MeRIP-seq 和 RT-PCR 与正常口腔上皮细胞 HOEC 和口腔癌细胞 SCC-9 相比,癌前阶段的调节剂表达。与HOEC细胞相比,我们在DOK细胞中发现了1180个高甲基化和1606个低甲基化m 6 A峰和354个具有不同m 6 A峰的差异表达mRNA。尽管 DOK 细胞中 m 6 A 修饰的变化小于 SCC-9 细胞,但两种细胞系中具有差异 m 6 A 的 mRNA 富集到许多相同的 GO 术语和 KEGG 通路中。在 20 个已知的 m 6中调节基因FTO、ALKBH5、METTL3和VIRMA在DOK细胞中上调或下调,METTL14/16、FTO和IGF2BP2/3等10个基因在SCC-9细胞中的表达水平发生显着变化。我们的数据表明,癌前细胞在一定程度上表现出m 6 A 修饰的变化。在癌前阶段确定一些关键的m 6 A 靶点和相应的调节因子,可能为未来通过表观遗传修饰预防癌症发展提供潜在的干预靶点。

更新日期:2022-09-28
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