文章：

解析非编码RNA在致癌和转移中对多功能NEDD4家族机制调控的复杂网络：从细胞培养研究到动物模型

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models

原文发布日期：4 August 2023

DOI: 10.3390/cancers15153971

类型: Review

开放获取: 是

英文摘要：

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the “ubiquitinome” is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.

摘要翻译： 

关于泛素化一个引人入胜特征的发现，促使人们对恶性细胞中的泛素化模式进行了详细分析。在多阶段癌变过程中，“泛素组”如何重塑已成为研究热点。有关NEDD4（神经前体细胞发育下调表达蛋白-4）结构和功能特征的开创性研究，将我们的认知巩固至新的成熟层面。此外，非编码RNA的调控作用进一步复杂化了非编码RNA与NEDD4家族成员之间错综复杂的相互作用网络。这些机制涵盖从miRNA介导的NEDD4家族成员靶向调控，到更广泛非编码RNA的转录因子调控。值得注意的是，NEDD4介导的不同蛋白降解过程受到lncRNA和circRNA的调控，而circRNA同样调控着miRNA对NEDD4家族成员的靶向作用。在识别NEDD4家族不同底物及全面解析其催化底物泛素化的分子机制方面，研究已取得重大进展。本综述旨在总结NEDD4家族在癌症生物学中的多功能角色，以及不同非编码RNA如何通过调控这些家族成员来影响癌症进程。未来的分子研究应致力于拓展药物设计空间，扩大可用于抑制/预防转移的靶点范围。

原文链接：

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models