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文献精选 > 近年高分"AI药物发现"研究（IF≥30，近5年）

m6A modification: recent advances, anticancer targeted drug discovery and beyond. ​

文献信息 ​

DOI10.1186/s12943-022-01510-2
PMID35164788
期刊Molecular cancer
影响因子33.9
JCR 分区Q1
发表年份2022
被引次数193
关键词癌症, 化学合成, 药物发现, 调节剂, 天然产物
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1476-4598
页码52
期号21(1)
作者Li-Juan Deng, Wei-Qing Deng, Shu-Ran Fan, Min-Feng Chen, Ming Qi, Wen-Yu Lyu, Qi Qi, Amit K Tiwari, Jia-Xu Chen, Dong-Mei Zhang, Zhe-Sheng Chen

一句话小结 ​

本研究综述了N6-甲基腺苷（m6A）修饰在癌症进展中的关键作用及其作为抗癌药物靶点的潜力，强调了从传统医学和现代药物开发中寻找m6A靶向抗癌剂的重要性。同时，提出人工智能在药物发现中的应用将进一步推动m6A靶向抗癌药物的研发进程。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

癌症 · 化学合成 · 药物发现 · 调节剂 · 天然产物

摘要 ​

异常的N6-甲基腺苷（m6A）修饰与癌症的发生、发展、进展和预后密切相关，异常的m6A调节因子已被确定为新型抗癌药物靶点。传统医学相关的方法和现代药物发现平台均已被用于开发针对m6A的药物。在此，我们更新了关于m6A修饰的最新研究发现，以及m6A修饰在癌症进展中的关键作用，并总结了从传统医学和基于计算的化学合成化合物中发现m6A靶向抗癌剂的合理来源。本综述强调了针对m6A修饰的潜在抗癌剂，并提出人工智能（AI）在发现m6A靶向抗癌药物方面的优势。m6A靶向抗癌药物发现的三个阶段包括：基于传统医学的天然产物、现代化学修饰或合成，以及未来的人工智能（AI）辅助方法。

英文摘要 ​

Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.

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主要研究问题 ​

  1. m6A修饰在癌症治疗中的具体机制是什么？
  2. 除了人工智能，还有哪些现代技术可以促进m6A靶向药物的发现？
  3. 传统医学中的哪些成分被证明对m6A修饰有影响？
  4. m6A修饰与癌症预后之间的关系如何？
  5. 在m6A靶向药物的开发中，面临哪些主要挑战和机遇？

核心洞察 ​

研究背景和目的 ​

N6-甲基腺苷（m6A）修饰是最常见的真核生物信使RNA（mRNA）修饰，已被证实与癌症的发生、发展、进展及预后密切相关。近年来，m6A调节因子被识别为新的抗癌药物靶点，研究旨在总结m6A修饰在癌症进展中的关键作用及其在抗癌药物发现中的应用，包括传统药物和现代药物发现平台的结合。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，系统总结了m6A修饰的最新进展和m6A调节因子在不同癌症中的作用。主要研究内容包括：

  1. m6A修饰的分子组成及其调节机制。
  2. m6A调节因子在癌症中的双重作用（既可作为肿瘤促进因子，也可作为肿瘤抑制因子）。
  3. 从传统药物和计算机辅助合成化合物中发现m6A靶向抗癌药物的策略。
  4. 人工智能（AI）在m6A靶向药物发现中的应用。

以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  • m6A修饰通过调节RNA的加工、翻译和稳定性，在癌症的多种生物过程中发挥重要作用。
  • m6A调节因子（如METTL3、FTO、YTHDF家族）在不同类型癌症中表现出双重角色，既可促进肿瘤进展，也可抑制肿瘤。
  • 传统药物中的天然产物如姜黄素、白藜芦醇等，已显示出对m6A调节因子的抑制作用。
  • AI技术的应用使得在药物发现中提高了效率和准确性。

主要结论/意义/创新性 ​

m6A修饰的异常与多种癌症的进展和患者预后密切相关，因此，靶向m6A修饰的药物开发具有重要的临床意义。通过结合传统药物和现代药物发现平台，尤其是利用AI技术，可以更高效地发现新的抗癌药物。研究强调了m6A调节因子作为潜在药物靶点的重要性。

研究局限性和未来方向 ​

尽管已有多种m6A调节因子被识别为药物靶点，但目前只有少数已进入临床试验阶段。未来的研究应集中于：

  • 提高m6A靶向药物的特异性和疗效。
  • 加强对m6A修饰机制的理解，以便开发更有效的治疗策略。
  • 探索更多天然产物和现代合成化合物的结合，以丰富m6A靶向药物库。

参考文献 ​

  1. FTO-Dependent N 6-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. - Hao Huang;Yinu Wang;Manoj Kandpal;Guangyuan Zhao;Horacio Cardenas;Yanrong Ji;Anusha Chaparala;Edward J Tanner;Jianjun Chen;Ramana V Davuluri;Daniela Matei - Cancer research (2020)
  2. AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. - Yuko Ueda;Ikumi Ooshio;Yasuyuki Fusamae;Kaori Kitae;Megumi Kawaguchi;Kentaro Jingushi;Hiroaki Hase;Kazuo Harada;Kazumasa Hirata;Kazutake Tsujikawa - Scientific reports (2017)
  3. Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. - Jie Yu;Peiwei Chai;Minyue Xie;Shengfang Ge;Jing Ruan;Xianqun Fan;Renbing Jia - Genome biology (2021)
  4. Novel Small Molecule RNA m6A Demethylase AlkBH5 Inhibitors for Treating Cancer. - Ram W Sabnis - ACS medicinal chemistry letters (2021)
  5. m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression. - Panpan Zhang;Qiuping He;Yuan Lei;Yingqin Li;Xin Wen;Mengzhi Hong;Jian Zhang;Xianyue Ren;Yaqin Wang;Xiaojing Yang;Qingmei He;Jun Ma;Na Liu - Cell death & disease (2018)
  6. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis. - Phillip J Hsu;Yunfei Zhu;Honghui Ma;Yueshuai Guo;Xiaodan Shi;Yuanyuan Liu;Meijie Qi;Zhike Lu;Hailing Shi;Jianying Wang;Yiwei Cheng;Guanzheng Luo;Qing Dai;Mingxi Liu;Xuejiang Guo;Jiahao Sha;Bin Shen;Chuan He - Cell research (2017)
  7. The FTO/miR-181b-3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer. - Yuanyuan Xu;Shuang Ye;Nan Zhang;Shuhui Zheng;Huatao Liu;Kewen Zhou;Ling Wang;Yue Cao;Peng Sun;Tinghuai Wang - Cancer communications (London, England) (2020)
  8. m6 A RNA methylation: from mechanisms to therapeutic potential. - P Cody He;Chuan He - The EMBO journal (2021)
  9. DMDRMR-Mediated Regulation of m6A-Modified CDK4 by m6A Reader IGF2BP3 Drives ccRCC Progression. - Yinmin Gu;Shaoxi Niu;Yang Wang;Liqiang Duan;Yongbo Pan;Zhou Tong;Xu Zhang;Zhenyu Yang;Bo Peng;Xiaodong Wang;Xiaoqi Han;Yuxin Li;Tianyou Cheng;Yajuan Liu;Lina Shang;Tongfeng Liu;Xiwang Yang;Minxuan Sun;Siyuan Jiang;Chang Zhang;Ning Zhang;Qinong Ye;Shan Gao - Cancer research (2021)
  10. Chemical inhibitors make their RNA epigenetic mark. - Megan Cully - Nature reviews. Drug discovery (2019)

引用本文的文献 ​

  1. m6A Regulator-Mediated Methylation Modification Patterns and Characteristics in COVID-19 Patients. - Xin Qing;Qian Chen;Ke Wang - Frontiers in public health (2022)
  2. Construction of a Prognostic Model for KIRC and Identification of Drugs Sensitive to Therapies - A Comprehensive Biological Analysis Based on m6A-Related LncRNAs. - Dian Xia;Qi Liu;Songbai Yan;Liangkuan Bi - Frontiers in oncology (2022)
  3. Novel insights into the interaction between N6-methyladenosine methylation and noncoding RNAs in musculoskeletal disorders. - Juanjuan Han;Hui Kong;Xueqiang Wang;Xin-An Zhang - Cell proliferation (2022)
  4. Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance. - Hong Lin;Yuxi Wang;Pinghan Wang;Fangyi Long;Ting Wang - Molecular cancer (2022)
  5. Microarray and bioinformatic analysis reveal the parental genes of m6A modified circRNAs as novel prognostic signatures in colorectal cancer. - Wenken Liang;Liyuan Deng;Chune Mo;Wei Chen;Yu Sha;Jianling Shi;Xianliang Hou;Yuping Zhang;Min Yang;Minglin Ou - Frontiers in oncology (2022)
  6. Physio-pathological effects of N6-methyladenosine and its therapeutic implications in leukemia. - Wei-Wei Liu;Hao Wang;Xiao-Yu Zhu - Biomarker research (2022)
  7. A Novel hepatocellular carcinoma specific hypoxic related signature for predicting prognosis and therapeutic responses. - Guangzhen Cai;Jinghan Zhu;Deng Ning;Ganxun Li;Yuxin Zhang;Yixiao Xiong;Junnan Liang;Chengpeng Yu;Xiaoping Chen;Huifang Liang;Zeyang Ding - Frontiers in immunology (2022)
  8. Analysis of m6A-related signatures associated with the tumor immune microenvironment and predict survival in acute myeloid leukemia. - Shushu Yuan;Zhirong Cong;Jiali Ji;Li Zhu;Qi Jiang;Ying Zhou;Qian Shen;Daniela Damiani;Xiaohong Xu;Bingzong Li - Annals of translational medicine (2022)
  9. Implications of m6A methylation and microbiota interaction in non-small cell lung cancer: From basics to therapeutics. - Fen-Sheng Qiu;Jia-Qi He;Yu-Sen Zhong;Mei-Ying Guo;Chen-Huan Yu - Frontiers in cellular and infection microbiology (2022)
  10. Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy. - Wenhao Liao;Yuchen Li;Jing Wang;Maoyuan Zhao;Nianzhi Chen;Qiao Zheng;Lina Wan;Yu Mou;Jianyuan Tang;Zhilei Wang - International journal of nanomedicine (2022)

... (183 更多 篇文献)

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