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人类癌症中长链非编码RNA/微小RNA- DNA甲基转移酶1轴的综合综述:作用机制与临床应用

A Comprehensive Review on LncRNAs/miRNAs-DNMT1 Axis in Human Cancer: Mechanistic and Clinical Application.

作者信息

Aghaei-Zarch Seyed Mohsen, Esmaeili Ali, Bagheri-Mohammadi Saeid

机构信息

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Student Research Committee, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Mol Med. 2025 May;29(10):e70604. doi: 10.1111/jcmm.70604.

Abstract

Cancer constitutes a significant public health concern, and addressing the challenge of cancer holds paramount importance and requires immediate attention. Epigenetic alterations, encompassing DNA methylation, have emerged as pivotal contributors to the development of diverse cancer types. These modifications exert their influence by modulating chromatin structure, gene expression patterns and other nuclear processes, thereby influencing cancer pathogenesis. Over the last two decades, an increasing body of evidence has established the involvement of DNA methyltransferase 1 (DNMT1) in various aspects of cancer development, including tumorigenesis, aggressiveness and treatment response. Furthermore, non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are increasingly recognised as significant modulators in diverse biological processes, encompassing metastasis, apoptosis, cell proliferation and differentiation. Several recent studies have elucidated the intricate relationship between epigenetic machinery, specifically DNMT1, and the expression of ncRNAs in the context of cancer. In this review, we provide a comprehensive overview of the interaction between DNMT1 and ncRNAs in cancer pathogenesis. Furthermore, we discuss the important role of the ncRNAs-DNMT1 axis in cancer stem cells and cancer therapy resistance as critical issues in cancer therapy. Finally, we demonstrate that herbal medicine and synthetic RNA molecules regulate DNMT1 activity and hold great promise in cancer treatment.

摘要

癌症是一个重大的公共卫生问题,应对癌症挑战至关重要且刻不容缓。包括DNA甲基化在内的表观遗传改变已成为多种癌症类型发展的关键因素。这些修饰通过调节染色质结构、基因表达模式和其他核过程发挥作用,从而影响癌症的发病机制。在过去二十年中,越来越多的证据表明DNA甲基转移酶1(DNMT1)参与癌症发展的各个方面,包括肿瘤发生、侵袭性和治疗反应。此外,非编码RNA(ncRNA),如微小RNA(miRNA)和长链非编码RNA(lncRNA),越来越被认为是多种生物学过程中的重要调节因子,包括转移、凋亡、细胞增殖和分化。最近的几项研究阐明了表观遗传机制,特别是DNMT1,与癌症背景下ncRNA表达之间的复杂关系。在这篇综述中,我们全面概述了DNMT1与ncRNA在癌症发病机制中的相互作用。此外,我们讨论了ncRNA-DNMT1轴在癌症干细胞和癌症治疗耐药性中的重要作用,这是癌症治疗中的关键问题。最后,我们证明草药和合成RNA分子可调节DNMT1活性,在癌症治疗中具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1171/12087000/028557982ffc/JCMM-29-e70604-g002.jpg

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