Mandhair Harpreet K, Novak Urban, Radpour Ramin
Department for BioMedical Research, University of Bern, Bern 3008, Switzerland.
World J Stem Cells. 2021 Jun 26;13(6):542-567. doi: 10.4252/wjsc.v13.i6.542.
Aberrant epigenetic alterations play a decisive role in cancer initiation and propagation the regulation of key tumor suppressor genes and oncogenes or by modulation of essential signaling pathways. Autophagy is a highly regulated mechanism required for the recycling and degradation of surplus and damaged cytoplasmic constituents in a lysosome dependent manner. In cancer, autophagy has a divergent role. For instance, autophagy elicits tumor promoting functions by facilitating metabolic adaption and plasticity in cancer stem cells (CSCs) and cancer cells. Moreover, autophagy exerts pro-survival mechanisms to these cancerous cells by influencing survival, dormancy, immunosurveillance, invasion, metastasis, and resistance to anti-cancer therapies. In addition, recent studies have demonstrated that various tumor suppressor genes and oncogenes involved in autophagy, are tightly regulated different epigenetic modifications, such as DNA methylation, histone modifications and non-coding RNAs. The impact of epigenetic regulation of autophagy in cancer cells and CSCs is not well-understood. Therefore, uncovering the complex mechanism of epigenetic regulation of autophagy provides an opportunity to improve and discover novel cancer therapeutics. Subsequently, this would aid in improving clinical outcome for cancer patients. In this review, we provide a comprehensive overview of the existing knowledge available on epigenetic regulation of autophagy and its importance in the maintenance and homeostasis of CSCs and cancer cells.
异常的表观遗传改变在癌症的起始和发展中起决定性作用，其作用方式包括调控关键的肿瘤抑制基因和癌基因，或调节重要的信号通路。自噬是一种高度调控的机制，以溶酶体依赖的方式对多余和受损的细胞质成分进行循环利用和降解。在癌症中，自噬具有不同的作用。例如，自噬通过促进癌症干细胞（CSCs）和癌细胞的代谢适应和可塑性发挥肿瘤促进功能。此外，自噬通过影响存活、休眠、免疫监视、侵袭、转移以及对抗癌治疗的抗性，对这些癌细胞发挥促存活机制。此外，最近的研究表明，参与自噬的各种肿瘤抑制基因和癌基因受到不同表观遗传修饰的严格调控，如DNA甲基化、组蛋白修饰和非编码RNA。自噬的表观遗传调控对癌细胞和CSCs的影响尚未完全了解。因此，揭示自噬表观遗传调控的复杂机制为改进和发现新型癌症治疗方法提供了机会。随后，这将有助于改善癌症患者的临床结局。在本综述中，我们全面概述了关于自噬表观遗传调控的现有知识及其在CSCs和癌细胞的维持及稳态中的重要性。
