Molecular insights and emerging therapeutic perspectives of the lncRNA GAS5/miR-21 axis in cancer, fibrosis, cardiovascular, and immune disorders

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research Pub Date : 2025-07-01 DOI:10.1016/j.mrrev.2025.108551

Salma M.S. Ahmad , Fatemeh Abdullah M. Ahmadi , Roberta Giordo , Gavino Casu , Gheyath K. Nasrallaha , Hatem Zayed , Gianfranco Pintus

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引用次数: 0

Abstract

Non-coding RNAs (ncRNAs) have redefined the complexity of gene regulation, with the long non-coding (lncRNA) GAS5/miR-21 axis emerging as a critical determinant of cell fate across diverse pathological contexts. This review examines the molecular mechanisms by which GAS5 regulates miR-21 activity, thereby restoring tumor suppressor networks and controlling key pathways, including the PI3K/AKT, MAPK/ERK, and Wnt/β-catenin pathways. We detail how dysregulation of this axis fuels cancer progression, metastasis, therapy resistance, fibrosis, cardiovascular diseases, osteoporosis, osteoarthritis, and autoimmune conditions like systemic lupus erythematosus. Beyond its role as a master regulator of apoptosis, proliferation, and EMT, the GAS5/miR-21 interaction holds immense promise as a therapeutic target and a liquid biopsy biomarker. However, clinical translation demands solutions to major challenges, including RNA delivery barriers, context-dependent effects, and adaptive resistance. Leveraging multi-omics integration, gene-editing technologies, and personalized RNA therapeutics will be pivotal to overcoming these obstacles. By critically integrating current knowledge and outlining future directions, this review positions the GAS5/miR-21 axis at the forefront of next-generation ncRNA therapeutics. Harnessing its full potential could not only revolutionize treatment paradigms but also transform our understanding of RNA-driven disease networks.

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lncRNA GAS5/miR-21轴在癌症、纤维化、心血管和免疫疾病中的分子见解和新兴治疗观点

非编码rna （ncrna）重新定义了基因调控的复杂性，长非编码（lncRNA） GAS5/miR-21轴在不同病理背景下成为细胞命运的关键决定因素。本文综述了GAS5调节miR-21活性的分子机制，从而恢复肿瘤抑制网络和控制关键通路，包括PI3K/AKT、MAPK/ERK和Wnt/β-catenin通路。我们详细介绍了该轴的失调如何促进癌症进展、转移、治疗抵抗、纤维化、心血管疾病、骨质疏松症、骨关节炎和系统性红斑狼疮等自身免疫性疾病。除了作为细胞凋亡、增殖和EMT的主要调节因子外，GAS5/miR-21相互作用作为治疗靶点和液体活检生物标志物具有巨大的前景。然而，临床翻译需要解决主要挑战，包括RNA传递障碍、上下文依赖效应和适应性抗性。利用多组学整合、基因编辑技术和个性化RNA疗法将是克服这些障碍的关键。通过批判性地整合当前知识和概述未来方向，本综述将GAS5/miR-21轴定位于下一代ncRNA治疗的前沿。充分利用它的潜力不仅可以彻底改变治疗模式，还可以改变我们对rna驱动的疾病网络的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Reviews in Mutation Research 生物-毒理学

CiteScore

12.20

自引率

1.90%

发文量

审稿时长

15.7 weeks

期刊介绍： The subject areas of Reviews in Mutation Research encompass the entire spectrum of the science of mutation research and its applications, with particular emphasis on the relationship between mutation and disease. Thus this section will cover advances in human genome research (including evolving technologies for mutation detection and functional genomics) with applications in clinical genetics, gene therapy and health risk assessment for environmental agents of concern.