Systematic Investigation of mRNA N (6)-Methyladenosine Machinery in Primary Prostate Cancer.
Systematic Investigation of mRNA N (6)-Methyladenosine Machinery in Primary Prostate Cancer.
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原发性前列腺癌 mRNA N6-甲基腺苷机制的系统研究
DOI：
10.1155/2020/8833438
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Jiang M;Lu Y;Duan D;Wang H;Man G;Kang C;Abulimiti K;Li Y
背景：令人赞赏的发现指出了N6-甲基腺苷（m6 A）机制在癌症发病和进展中的关键作用。然而，在前列腺癌领域的相关研究方面所做的努力有限。方法通过PubMed检索获得mRNA m6 A机器的组成部分。进行多组学整合以系统地研究原发性前列腺癌中的mRNA m6 A机制。此外，进行了两种预后m6 A阅读器EIF 3D和HNRNPA 2B 1的RNA干扰测定，以探索它们在前列腺癌细胞增殖和迁移中的功能对m6 A的依赖性。结果迄今为止，共鉴定出41个m6 A mRNA调节子。在前列腺肿瘤的调节因子中观察到小程度的拷贝数畸变和极低频率的体细胞突变。m6 A基因表达调控机制中CpG位点的富集和DNA甲基化的广泛改变，拷贝数变异对m6 A调控基因表达的影响强于DNA甲基化紊乱。此外，我们的研究确定了一组与临床特征和/或生存相关的m6 A调节因子，主要是m6 A结合蛋白。翻译起始因子亚基EIF 3D和剪接因子HNRNPA 2B 1可以是独立的预后因子，其可能通过影响癌症相关过程（例如细胞周期）而分别有助于延缓和促进癌症进展。此外，体外试验表明，m6 A影响EIF 3D和HNRNPA 2B 1在前列腺癌细胞增殖和迁移中的作用。结论本研究系统描述了m6 A mRNA表达机制的分子特征及其在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m6 A系统铺平道路。
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.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1098/rstb.2016.0176
发表时间：
2017-03-19
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Cate JH
通讯作者：
Cate JH
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
通过小鼠和人 FTO 对单链 DNA 和 RNA 中的 3-甲基胸腺嘧啶和 3-甲基尿嘧啶进行氧化去甲基化。
影响因子：
3.5
作者：
Jia, Guifang;Yang, Cai-Guang;Yang, Shangdong;Jian, Xing;Yi, Chengqi;Zhou, Zhiqiang;He, Chuan
通讯作者：
He, Chuan
影响因子：
64.5
作者：
Meyer KD;Patil DP;Zhou J;Zinoviev A;Skabkin MA;Elemento O;Pestova TV;Qian SB;Jaffrey SR
通讯作者：
Jaffrey SR