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癌症中的假尿苷合酶7:功能、机制及治疗潜力

Pseudouridine Synthase 7 in Cancer: Functions, Mechanisms, and Therapeutic Potential.

作者信息

Yang Qiwei, Boyer Thomas G, Al-Hendy Ayman

机构信息

Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA.

Department of Molecular Medicine, UT Health San Antonio, San Antonio, TX 78229, USA.

出版信息

Cells. 2025 Sep 4;14(17):1380. doi: 10.3390/cells14171380.

Abstract

Pseudouridylation, the most abundant RNA modification, plays a critical role in modulating RNA structure, stability, and function. Among the family of pseudouridine synthases, Pseudouridine Synthase 7 (PUS7) has recently gained attention for its emerging roles in human health and disease. Originally characterized for its function in modifying tRNA and small non-coding RNAs, PUS7 is now recognized as a dynamic regulator of mRNA pseudouridylation, influencing gene expression at the post-transcriptional level. Aberrant expressions or activity of PUS7 have been linked to a variety of pathological conditions, including cancers such as colon cancer, glioblastoma, pancreatic cancer, and neuroblastoma, as well as potential roles in neurodevelopmental disorders and immune regulation. Through mechanisms involving translational reprogramming, stress adaptation, and epitranscriptomic remodeling, PUS7 contributes to disease progression and cellular plasticity. This review summarizes the current understanding of PUS7 biology, its functional relevance in the contexts of cancer progression, and the growing interest in targeting RNA-modifying enzymes for therapeutic intervention. Uncovering the full spectrum of PUS7-mediated pseudouridylation and its downstream effects holds promise for advancing our understanding of RNA-based regulation in human diseases, including gynecological disorders.

摘要

假尿苷化是最丰富的RNA修饰,在调节RNA结构、稳定性和功能方面发挥着关键作用。在假尿苷合成酶家族中,假尿苷合成酶7(PUS7)因其在人类健康和疾病中的新作用最近受到关注。PUS7最初因其在修饰tRNA和小非编码RNA中的功能而被描述,现在被认为是mRNA假尿苷化的动态调节因子,在转录后水平影响基因表达。PUS7的异常表达或活性与多种病理状况有关,包括结肠癌、胶质母细胞瘤、胰腺癌和神经母细胞瘤等癌症,以及在神经发育障碍和免疫调节中的潜在作用。通过涉及翻译重编程、应激适应和表转录组重塑的机制,PUS7促进疾病进展和细胞可塑性。本综述总结了目前对PUS7生物学的理解、其在癌症进展背景下的功能相关性,以及针对RNA修饰酶进行治疗干预的兴趣日益增加。揭示PUS7介导的假尿苷化的全貌及其下游效应有望增进我们对包括妇科疾病在内的人类疾病中基于RNA的调节的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93c1/12428485/eb37fddc1f68/cells-14-01380-g001.jpg

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