Background. Appreciable findings have pointed out pivotal roles of N⁶-methyladenosine (m⁶A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. Methods. A PubMed search was conducted to acquire components of the mRNA m⁶A machinery. Multiomics integration was performed to systematically investigate the mRNA m⁶A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m⁶A readers EIF3D and HNRNPA2B1 were conducted to explore m⁶A dependence of their functions in prostate cancer cell proliferation and migration. Results. A total of 41 mRNA m⁶A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m⁶A machinery were also found. Impact of copy number variation on m⁶A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m⁶A regulators related to clinical features and/or survival which were largely m⁶A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m⁶A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions. Our report systematically described molecular features of the mRNA m⁶A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m⁶A system in prostate cancer.

中文翻译：

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原发性前列腺癌中 mRNA N6-甲基腺苷机制的系统研究

背景。可观的发现指出了N ⁶ -甲基腺苷 (m ⁶ A) 机制在癌症发作和进展中的关键作用。然而，针对前列腺癌领域的相关研究的努力有限。方法。进行了 PubMed 搜索以获取 mRNA m ⁶ A 机器的组件。进行多组学整合以系统地研究原发性前列腺癌中的 mRNA m ⁶ A 机制。^{此外，对两个预后 m 6} A 阅读器 EIF3D 和 HNRNPA2B1 进行RNA 干扰测定以探索 m ⁶它们在前列腺癌细胞增殖和迁移中的功能依赖性。结果。迄今为止，已鉴定出总共 41 个 mRNA m ^{6 A 调节剂。}在整个前列腺肿瘤的调节剂中观察到少量拷贝数异常和极低频率的体细胞突变。还发现了 m ⁶ A 机器中 CpG 位点的富集和 DNA 甲基化的广泛变化。拷贝数变异对 m ⁶ A 调节子表达的影响比 DNA 甲基化干扰更强。此外，我们的研究确定了一组与临床特征和/或存活率相关的 m ⁶ A 调节因子，这些调节因子主要是 m ⁶A结合蛋白。翻译起始因子亚基 EIF3D 和剪接因子 HNRNPA2B1 可以是独立的预后因素，它们可能通过影响细胞周期等癌症相关过程分别促进癌症进展的延缓和促进。此外，体外试验表明，m ⁶ A 影响了 EIF3D 和 HNRNPA2B1 在前列腺癌细胞增殖和迁移中的作用。结论。^{我们的报告系统地描述了 mRNA m 6} A 机制的分子特征及其在原发性前列腺癌中的潜在作用。从这项工作中获得的知识可能为进一步研究前列腺癌中的 m ⁶ A 系统铺平道路。