Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China; National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China.
Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Biomed Pharmacother. 2024 Apr;173:116372. doi: 10.1016/j.biopha.2024.116372. Epub 2024 Mar 2.
An increasing number of studies have shown that FAM83A, a member of the family with sequence similarity 83 (FAM83), which consists of eight members, is a key tumor therapeutic target involved in multiple signaling pathways. It has been reported that FAM83A plays essential roles in the regulation of Wnt/β-catenin, EGFR, MAPK, EMT, and other signaling pathways and physiological processes in models of pancreatic cancer, lung cancer, breast cancer, and other malignant tumors. Moreover, the expression of FAM83A could be significantly affected by multiple noncoding RNAs that are dysregulated in malignant tumors, the dysregulation of which is essential for the malignant process. Among these noncoding RNAs, the most noteworthy is the antisense long noncoding (Lnc) RNA of FAM83A itself (FAM83A-AS1), indicating an outstanding synergistic carcinogenic effect between FAM83A and FAM83A-AS1. In the present study, the specific mechanisms by which FAM83A and FAM83A-AS1 cofunction in the Wnt/β-catenin and EGFR signaling pathways were reviewed in detail, which will guide subsequent research. We also described the applications of FAM83A and FAM83A-AS1 in tumor therapy and provided a certain theoretical basis for subsequent drug target development and combination therapy strategies.
越来越多的研究表明,FAM83A(家族与序列相似性 83 成员,FAM83)是一个关键的肿瘤治疗靶点,它包含 8 个成员,涉及多个信号通路。有报道称,FAM83A 在胰腺癌、肺癌、乳腺癌等恶性肿瘤模型中的 Wnt/β-catenin、EGFR、MAPK、EMT 等信号通路和生理过程的调节中发挥着重要作用。此外,FAM83A 的表达可以被多种在恶性肿瘤中失调的非编码 RNA 显著影响,这些失调对于恶性过程至关重要。在这些非编码 RNA 中,最值得注意的是 FAM83A 自身的反义长非编码 RNA(FAM83A-AS1),这表明 FAM83A 和 FAM83A-AS1 之间存在着突出的协同致癌作用。在本研究中,详细综述了 FAM83A 和 FAM83A-AS1 如何在 Wnt/β-catenin 和 EGFR 信号通路中协同作用的具体机制,这将为后续的研究提供指导。我们还描述了 FAM83A 和 FAM83A-AS1 在肿瘤治疗中的应用,为后续的药物靶点开发和联合治疗策略提供了一定的理论基础。