转录组范围分析鉴定出与结肠癌相关的 m6A 转录本和潜在的 RNA 甲基化修饰因子。
Transcriptome-wide profiling identifies colon cancer-associated m6A transcripts and potential RNA methyl modifiers.
机构信息
Department of Molecular Oncology, Cancer Institute (W.I.A), Chennai, Tamil Nadu, 600036, India.
Department of Surgical Oncology, Cancer Institute (W.I.A), Chennai, Tamil Nadu, 600036, India.
出版信息
Mol Biol Rep. 2024 Feb 12;51(1):299. doi: 10.1007/s11033-024-09217-x.
BACKGROUND
N6-methyladenosine (m6A) is a prevalent and crucial RNA methylation modification that plays a significant role in various biological and pathological processes. The dysregulation of m6A has been linked to the initiation, progression, and metastasis of several cancer types, including colon cancer. The transcriptome of colon cancer indeed provides insight into dysregulated coding and non-coding RNAs, but it does not reveal the mechanisms, such as m6A modifications, that determine post-transcriptional and pre-translational regulations. This study using MeRIP sequencing aims to explain the distribution of m6A modification across altered gene expression and its association with colon cancer.
METHODS AND RESULTS
The levels of m6A in different colon cancer cell lines were quantified and correlated with the expression of m6A modifiers such as writers, readers, and erasers. Our results showed that global m6A levels in colon cancer were associated with METTL14, YTHDF2, and YTHDC1. We performed Epi-transcriptome profiling of m6A in colon cancer cell lines using Methylated RNA Immunoprecipitation (MeRIP) sequencing. The differential methylation analysis revealed 7312 m6A regions among the colon cancer cell lines. Our findings indicated that the m6A RNA methylation modifications were mainly distributed in the last exonic and 3' untranslated regions. We also discovered that non-coding RNAs such as miRNA, lncRNA, and circRNA carry m6A marks. Gene set enrichment and motif analysis suggested a strong association of m6A with post-transcriptional events, particularly splicing control. Overall, our study sheds light on the potential role of m6A in colon cancer and highlights the importance of further investigation in this area.
CONCLUSION
This study reports m6A enrichment in the last exonic regions and 3' UTRs of mRNA transcripts in colon cancer. METTL14, YTHDF2, and YTHDC1 were the most significant modifiers in colon cancer cells. The functions of m6A-modified genes were found to be RNA methylation and RNA capping. Overall, the study illustrates the transcriptome-wide distribution of m6A and its eminent role in mRNA splicing and translation control of colon cancer.
背景
N6-甲基腺苷（m6A）是一种普遍存在且至关重要的 RNA 甲基化修饰，在各种生物和病理过程中发挥着重要作用。m6A 的失调与多种癌症类型的发生、发展和转移有关，包括结肠癌。结肠癌的转录组确实揭示了失调的编码和非编码 RNA，但它并没有揭示决定转录后和翻译前调控的机制，例如 m6A 修饰。本研究使用 MeRIP 测序旨在解释 m6A 修饰在改变基因表达中的分布及其与结肠癌的关联。
方法和结果
我们定量测定了不同结肠癌细胞系中的 m6A 水平，并将其与 m6A 修饰剂（如书写器、阅读器和橡皮擦）的表达进行了相关性分析。结果表明，结肠癌中整体 m6A 水平与 METTL14、YTHDF2 和 YTHDC1 相关。我们使用 Methylated RNA Immunoprecipitation（MeRIP）测序对结肠癌细胞系中的 m6A 进行了 Epi-transcriptome 分析。差异甲基化分析显示，在结肠癌细胞系中存在 7312 个 m6A 区域。我们的研究结果表明，m6A RNA 甲基化修饰主要分布在最后外显子和 3'非翻译区。我们还发现非编码 RNA（如 miRNA、lncRNA 和 circRNA）携带 m6A 标记。基因集富集和基序分析表明，m6A 与转录后事件，特别是剪接控制密切相关。总的来说，我们的研究揭示了 m6A 在结肠癌中的潜在作用，并强调了进一步研究这一领域的重要性。
结论
本研究报告了 m6A 在结肠癌中外显子区域和 3'UTR 中的富集。METTL14、YTHDF2 和 YTHDC1 是结肠癌细胞中最显著的修饰因子。m6A 修饰基因的功能是 RNA 甲基化和 RNA 加帽。总的来说，该研究说明了 m6A 在转录组范围内的分布及其在 mRNA 剪接和翻译控制中的重要作用。
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