泛癌症分析揭示不同癌症类型中的 m6A 变异和细胞特异性调控网络

Yao Lin, Jingyi Li, Shuaiyi Liang, Yaxin Chen, Yueqi Li, Yixian Cun, Lei Tian, Yuanli Zhou, Yitong Chen, Jiemei Chu, Hubin Chen, Qiang Luo, Ruili Zheng, Gang Wang, Hao Liang, Ping Cui, Sanqi An
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引用次数: 0

摘要

作为mRNA中最丰富的信使RNA(mRNA)修饰,N-6-甲基腺苷(m6A)在RNA命运中起着至关重要的作用,影响着各种肿瘤类型的细胞和生理过程。然而,我们对 m6A 甲基组在肿瘤异质性中的功能和作用的了解仍然有限。在此,我们从97个m6A测序(m6A-seq)和RNA测序样本中收集并分析了9种人体组织的m6A甲基组。我们的研究结果表明,与正常组织相比,m6A 在大多数肿瘤组织中表现出不同的异质性,这也是导致不同癌症类型临床结果各异的原因之一。我们还发现,在不同的癌症类型中,癌症特异性 m6A 水平调控着不同癌症相关基因的表达。利用一种名为 "m6A-express "的新型可靠方法,我们预测了受 m6A 调控的基因,并揭示了癌症特异性 m6A 调控基因对不同患者群体的预后、肿瘤起源和免疫细胞浸润水平的影响。此外,我们还发现了调控癌症特异性 m6A 的细胞特异性 m6A 调控因子,并构建了一个调控网络。实验验证证实,细胞特异性 m6A 调节因子 CAPRIN1 控制着 TP53 的 m6A 水平。总之,我们的研究揭示了不同肿瘤组织中 m6A 的临床相关性,并解释了这种异质性是如何形成的。这些结果进一步表明,m6A 有潜力为不同癌症类型的患者提供癌症精准医疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pan-cancer Analysis Reveals m6A Variation and Cell-specific Regulatory Network in Different Cancer Types.

As the most abundant messenger RNA (mRNA) modification, N6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing (RNA-seq) samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called "m6A-express", we predicted m6A-regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin, and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A in cancer precision medicine for patients with different cancer types.

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