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自噬在肿瘤细胞转化中的作用:一种潜在的新型治疗策略。

Autophagy in Cancer Cell Transformation: A Potential Novel Therapeutic Strategy.

机构信息

National Research Mordovia State University, Bolshevitskaya Street, 68, Saransk, Rep. Mordovia 430005, Russian Federation.

出版信息

Curr Cancer Drug Targets. 2022;22(9):749-756. doi: 10.2174/1568009622666220428102741.

Abstract

Basal autophagy plays a crucial role in maintaining intracellular homeostasis and prevents the cell from escaping the cell cycle regulation mechanisms and being cancerous. Mitophagy and nucleophagy are essential for cell health. Autophagy plays a pivotal role in cancer cell transformation, where upregulated precancerous autophagy induces apoptosis. Impaired autophagy has been shown to upregulate cancer cell transformation. However, tumor cells upregulate autophagy to escape elimination and survive the unfavorable conditions and resistance to chemotherapy. Cancer cells promote autophagy through modulation of autophagy regulation mechanisms and increase expression of the autophagyrelated genes. Whereas, autophagy regulation mechanisms involved microRNAs, transcription factors, and the internalized signaling pathways such as AMPK, mTOR, III PI3K, and ULK-1. Disrupted regulatory mechanisms are various as the cancer cell polymorphism. Targeting a higher level of autophagy regulation is more effective, such as gene expression, transcription factors, or epigenetic modification that are responsible for the up-regulation of autophagy in cancer cells. Currently, the CRISPR-CAS9 technique is available and can be applied to demonstrate the potential effects of autophagy in cancerous cells.

摘要

基础自噬在维持细胞内稳态方面起着至关重要的作用,可防止细胞逃避细胞周期调控机制并癌变。线粒体自噬和核自噬对细胞健康至关重要。自噬在癌细胞转化中起着关键作用,上调的癌前自噬可诱导细胞凋亡。自噬受损已被证明会促进癌细胞转化。然而,肿瘤细胞通过调节自噬调控机制并增加自噬相关基因的表达来促进自噬,以逃避清除并在不利条件和化疗耐药性下存活。癌细胞通过调节自噬调控机制和增加自噬相关基因的表达来促进自噬。而自噬调控机制涉及 microRNAs、转录因子以及内化的信号通路,如 AMPK、mTOR、III PI3K 和 ULK-1。由于癌细胞的多态性,破坏调控机制是多种多样的。针对更高水平的自噬调控更为有效,例如基因表达、转录因子或表观遗传修饰,这些都负责上调癌细胞中的自噬。目前,CRISPR-CAS9 技术已经可用,并可应用于证明自噬在癌细胞中的潜在作用。

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