Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Genetics, Tabriz, Iran.
Med Oncol. 2024 Nov 25;42(1):13. doi: 10.1007/s12032-024-02552-w.
Cytotoxic T lymphocyte antigen 4 (CTLA-4), in conjunction with PD-1 and CD28, plays a pivotal role in the modulation of T-cell activation. Specifically, CTLA-4 exerts its influence by impeding the generation of IL-2 and the proliferation of T cells. CTLA-4, being a receptor with a high affinity, engages in competitive binding with CD28 for the interaction with primary T-cell activator molecules, specifically CD80 and CD86. The appropriate functioning of T-cell activation is contingent upon maintaining a precise equilibrium between CTLA-4 and CD28. Consequently, any disruption in the expression of CTLA-4 significantly enhances the risk for a range of severe ailments, such as cancer, infectious diseases, allergies, and notably autoimmune diseases. The significance of epigenetic regulation of CTLA-4, particularly through non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has considerable weight within this particular framework. To date, there have been associations shown between various abnormalities in the expression of ncRNAs that regulate CTLA-4 and clinicopathological characteristics. Nevertheless, it is evident that there is a lack of a comprehensive investigation. Hence, the present work was undertaken to summarize the existing research on the epigenetic control of CTLA-4, with a primary emphasis on elucidating the regulatory procedures, biological processes, and clinical applications in human diseases. The objective of this review is to acquire a thorough comprehension of the relationship between RNA/lncRNA/miRNA/mRNA (CTLA-4) and its role in the progression of diverse human disorders.
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）与 PD-1 和 CD28 一起，在调节 T 细胞激活方面发挥着关键作用。具体来说，CTLA-4 通过阻碍 IL-2 的产生和 T 细胞的增殖来发挥作用。CTLA-4 作为一种高亲和力的受体，与 CD28 竞争结合，与原发性 T 细胞激活分子（特别是 CD80 和 CD86）相互作用。T 细胞激活的适当功能取决于 CTLA-4 和 CD28 之间保持精确平衡。因此，CTLA-4 表达的任何中断都会显著增加一系列严重疾病的风险，如癌症、传染病、过敏症，特别是自身免疫性疾病。CTLA-4 的表观遗传调控的重要性，特别是通过非编码 RNA（ncRNA），如 microRNAs（miRNAs）、长非编码 RNA（lncRNAs）和环状 RNA（circRNAs），在这一特定框架内具有相当大的分量。迄今为止，已经有研究表明，调节 CTLA-4 的 ncRNA 表达的各种异常与临床病理特征之间存在关联。然而，显然缺乏全面的调查。因此，本研究旨在总结 CTLA-4 的表观遗传调控的现有研究，主要强调阐明调节程序、生物学过程以及在人类疾病中的临床应用。本综述的目的是深入了解 RNA/lncRNA/miRNA/mRNA（CTLA-4）之间的关系及其在多种人类疾病进展中的作用。
