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膀胱癌中的表观遗传修饰:DNA甲基化与微小RNA之间的相互作用

Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs.

作者信息

Li Wei, Luo Peiyue, Chen Qi, Cheng Le, Gan Lifeng, Zhang Fangtao, Zhong Haidong, Zheng Liying, Qian Biao

机构信息

The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China.

Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.

出版信息

Front Immunol. 2025 Feb 5;16:1518144. doi: 10.3389/fimmu.2025.1518144. eCollection 2025.

Abstract

Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.

摘要

膀胱癌(BC)是一种以泌尿系统疾病高发病率为特征的恶性肿瘤。BC复杂的发病机制长期以来一直是医学研究的重点。随着表观遗传学的蓬勃发展,表观遗传修饰在BC发生和发展中的关键作用已得到阐明。这些修饰不仅影响基因表达,还影响肿瘤细胞的关键生物学行为,包括增殖、分化、凋亡、侵袭和转移。值得注意的是,DNA甲基化作为一种重要的表观遗传调控机制,在BC中常表现为特定基因启动子区域的整体低甲基化或高甲基化。这种甲基化模式的改变可导致基因组不稳定性增加,从而深刻影响原癌基因和抑癌基因的表达。微小RNA(miRNAs)作为非编码小RNA,通过调控靶基因参与BC的各种生物学过程。因此,本研究旨在探讨DNA甲基化与miRNAs在BC发生发展中的相互作用机制。研究表明,DNA甲基化不仅直接影响miRNA基因的表达,还通过调节miRNA启动子区域的甲基化状态间接影响miRNAs的成熟和功能。同时,miRNAs可通过靶向DNA甲基转移酶(DNMTs)等关键酶来调节DNA甲基化水平,从而建立一个复杂的反馈调控网络。深入了解BC中DNA甲基化与miRNAs之间的相互作用机制,将有助于阐明该疾病表观遗传修饰的复杂性和动态性,并可能为BC的早期诊断、治疗和预后评估提供新的分子靶点和策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97df/11841399/3c64a8b1cdf6/fimmu-16-1518144-g001.jpg

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