Zeng Shuyan, Zhou Zhiyong, Li Yi, Wu Di, Xiao Qiuyun, Peng Huiyun
Center for Molecular Diagnosis and Precision Medicine, The First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, China.
Huankui Academy, Nanchang University, Nanchang, China.
Front Immunol. 2025 May 2;16:1576674. doi: 10.3389/fimmu.2025.1576674. eCollection 2025.
The human PYHIN family proteins, including AIM2, IFI16, IFIX, and MNDA, which are crucial cytosolic nucleic acid sensors. These proteins share a common structural feature, including signature N-terminal PYD domain and C-terminal HIN-200 domain, which enable them to recognize intracellular nucleic acids and assemble inflammasomes, triggering inflammatory responses and programmed cell death. Over the last decade, it has emerged that the PYHIN family proteins play multifaceted roles in cancer biology, with dualistic roles due to tumor heterogeneity and the tumor microenvironment's plasticity through dependent or independent of inflammasome mechanisms. Here, we discuss their ability to function as both a tumor suppressor and a tumor promoter of tumor progression emphasizes the need for further research to delineate the precise mechanisms by which these proteins operate in various cancer contexts. Understanding these dynamics could pave the way for novel therapeutic approaches that harness the dual nature of PYHIN family members to improve cancer treatment outcomes.
人类PYHIN家族蛋白，包括AIM2、IFI16、IFIΧ和MNDA，它们是至关重要的胞质核酸传感器。这些蛋白具有共同的结构特征，包括标志性的N端PYD结构域和C端HIN-200结构域，这使它们能够识别细胞内核酸并组装炎性小体，引发炎症反应和程序性细胞死亡。在过去十年中，人们发现PYHIN家族蛋白在癌症生物学中发挥着多方面的作用，由于肿瘤异质性以及肿瘤微环境通过依赖或不依赖炎性小体机制的可塑性，它们具有双重作用。在此，我们讨论它们作为肿瘤进展的肿瘤抑制因子和肿瘤促进因子的功能，强调需要进一步研究以阐明这些蛋白在各种癌症背景下发挥作用的确切机制。了解这些动态变化可为利用PYHIN家族成员的双重性质改善癌症治疗结果的新型治疗方法铺平道路。
