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线粒体在癌症进展中充当关键调节因子:突变、线粒体动力学和治疗方法的当前概念。

Mitochondria act as a key regulatory factor in cancer progression: Current concepts on mutations, mitochondrial dynamics, and therapeutic approach.

机构信息

Chittaranjan National Cancer Institute, 37 S. P. Mukherjee Road, Kolkata 700026, India.

CSIR-IICB Translational Research Unit Of Excellence, CN-6, Salt Lake, Sector - V, Kolkata 700091, India.

出版信息

Mutat Res Rev Mutat Res. 2024 Jan-Jun;793:108490. doi: 10.1016/j.mrrev.2024.108490. Epub 2024 Mar 8.

Abstract

The diversified impacts of mitochondrial function vs. dysfunction have been observed in almost all disease conditions including cancers. Mitochondria play crucial roles in cellular homeostasis and integrity, however, mitochondrial dysfunctions influenced by alterations in the mtDNA can disrupt cellular balance. Many external stimuli or cellular defects that cause cellular integrity abnormalities, also impact mitochondrial functions. Imbalances in mitochondrial activity can initiate and lead to accumulations of genetic mutations and can promote the processes of tumorigenesis, progression, and survival. This comprehensive review summarizes epigenetic and genetic alterations that affect the functionality of the mitochondria, with considerations of cellular metabolism, and as influenced by ethnicity. We have also reviewed recent insights regarding mitochondrial dynamics, miRNAs, exosomes that play pivotal roles in cancer promotion, and the impact of mitochondrial dynamics on immune cell mechanisms. The review also summarizes recent therapeutic approaches targeting mitochondria in anti-cancer treatment strategies.

摘要

线粒体功能与功能障碍的多样化影响几乎在所有疾病状态中都有观察到,包括癌症。线粒体在细胞内稳态和完整性中起着至关重要的作用,然而,线粒体功能障碍受 mtDNA 改变的影响会破坏细胞平衡。许多外部刺激或导致细胞完整性异常的细胞缺陷也会影响线粒体功能。线粒体活性的失衡会引发并导致遗传突变的积累,并促进肿瘤发生、进展和存活的过程。本综述总结了影响线粒体功能的表观遗传和遗传改变,同时考虑了细胞代谢,并受种族影响。我们还回顾了最近关于线粒体动力学、miRNA、外泌体在促进癌症发生中发挥关键作用以及线粒体动力学对免疫细胞机制影响的新见解。该综述还总结了最近针对癌症治疗策略中靶向线粒体的治疗方法。

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