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miRNAs 与人类癌症中信号通路的串扰:潜在的治疗意义。

The crosstalk between miRNAs and signaling pathways in human cancers: Potential therapeutic implications.

机构信息

Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.

Department of Zoology, Magadh Mahila College, Patna University, Patna, India.

出版信息

Int Rev Cell Mol Biol. 2024;386:133-165. doi: 10.1016/bs.ircmb.2023.12.001. Epub 2024 Jan 23.

Abstract

MicroRNAs (miRNAs) are increasingly recognized as central players in the regulation of eukaryotic physiological processes. These small double stranded RNA molecules have emerged as pivotal regulators in the intricate network of cellular signaling pathways, playing significant roles in the development and progression of human cancers. The central theme in miRNA-mediated regulation of signaling pathways involves their ability to target and modulate the expression of pathway components. Aberrant expression of miRNAs can either promote or suppress key signaling events, influencing critical cellular processes such as proliferation, apoptosis, angiogenesis, and metastasis. For example, oncogenic miRNAs often promote cancer progression by targeting tumor suppressors or negative regulators of signaling pathways, thereby enhancing pathway activity. Conversely, tumor-suppressive miRNAs frequently inhibit oncogenic signaling by targeting key components within these pathways. This complex regulatory crosstalk underscores the significance of miRNAs as central players in shaping the signaling landscape of cancer cells. Furthermore, the therapeutic implications of targeting miRNAs in cancer are substantial. miRNAs can be manipulated to restore normal signaling pathway activity, offering a potential avenue for precision medicine. The development of miRNA-based therapeutics, including synthetic miRNA mimics and miRNA inhibitors, has shown promise in preclinical and clinical studies. These strategies aim to either enhance the activity of tumor-suppressive miRNAs or inhibit the function of oncogenic miRNAs, thereby restoring balanced signaling and impeding cancer progression. In conclusion, the crosstalk between miRNAs and signaling pathways in human cancers is a dynamic and influential aspect of cancer biology. Understanding this interplay provides valuable insights into cancer development and progression. Harnessing the therapeutic potential of miRNAs as regulators of signaling pathways opens up exciting opportunities for the development of innovative cancer treatments with the potential to improve patient outcomes. In this chapter, we provide an overview of the crosstalk between miRNAs and signaling pathways in the context of cancer and highlight the potential therapeutic implications of targeting this regulatory interplay.

摘要

微小 RNA(miRNAs)被越来越多地认为是真核生物生理过程调控的核心参与者。这些小的双链 RNA 分子已经成为细胞信号通路复杂网络中的关键调节剂,在人类癌症的发展和进展中发挥着重要作用。miRNA 介导的信号通路调控的核心主题涉及它们靶向和调节通路成分表达的能力。miRNA 的异常表达可以促进或抑制关键信号事件,影响细胞增殖、凋亡、血管生成和转移等关键细胞过程。例如,致癌 miRNA 通常通过靶向肿瘤抑制因子或信号通路的负调节剂来促进癌症进展,从而增强通路活性。相反,肿瘤抑制性 miRNA 通常通过靶向这些通路中的关键成分来抑制致癌信号。这种复杂的调控串扰突显了 miRNA 作为塑造癌细胞信号景观的核心参与者的重要性。此外,靶向 miRNA 在癌症中的治疗意义重大。可以操纵 miRNA 来恢复正常的信号通路活性,为精准医学提供了潜在途径。基于 miRNA 的治疗方法的开发,包括合成 miRNA 模拟物和 miRNA 抑制剂,在临床前和临床研究中显示出了前景。这些策略旨在增强肿瘤抑制性 miRNA 的活性或抑制致癌 miRNA 的功能,从而恢复平衡的信号并阻碍癌症进展。总之,miRNA 与人类癌症中的信号通路之间的串扰是癌症生物学中动态和有影响力的方面。理解这种相互作用为癌症的发生和发展提供了有价值的见解。利用 miRNA 作为信号通路调节剂的治疗潜力为开发创新的癌症治疗方法开辟了令人兴奋的机会,有望改善患者的治疗效果。在本章中,我们概述了 miRNA 与癌症中信号通路之间的串扰,并强调了靶向这种调控相互作用的潜在治疗意义。

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