Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
Free Radic Biol Med. 2019 Aug 1;139:1-15. doi: 10.1016/j.freeradbiomed.2019.05.017. Epub 2019 May 15.
To protect tissues and the organism from disease, potentially harmful cells are removed through programmed cell death processes, including apoptosis and necroptosis. These types of cell death are critically controlled by microRNAs (miRNAs). MiRNAs are short RNA molecules that target and inhibit expression of many cellular regulators, including those controlling programmed cell death via the intrinsic (Bcl-2 and Mcl-1), extrinsic (TRAIL and Fas), p53-and endoplasmic reticulum (ER) stress-induced apoptotic pathways, as well as the necroptosis cell death pathway. In this review, we discuss the current knowledge of apoptosis and necroptosis pathways and how these are impaired in cancer cells. We focus on how miRNAs disrupt apoptosis and necroptosis, thereby critically contributing to malignancy. Understanding which and how miRNAs and their targets affect cell death pathways could open up novel therapeutic opportunities for cancer patients. Indeed, restoration of pro-apoptotic tumor suppressor miRNAs (apoptomiRs) or inhibition of oncogenic miRNAs (oncomiRs) represent strategies that are currently being trialed or are already applied as miRNA-based cancer therapies. Therefore, better understanding the cancer type-specific expression of apoptomiRs and oncomiRs and their underlying mechanisms in cell death pathways will not only advance our knowledge, but also continue to provide new opportunities to treat cancer.
为了保护组织和机体免受疾病的侵害，通过程序性细胞死亡过程（包括细胞凋亡和细胞坏死）清除潜在的有害细胞。这些类型的细胞死亡受到 microRNAs (miRNAs) 的严格控制。miRNAs 是短的 RNA 分子，可靶向并抑制许多细胞调节剂的表达，包括通过内在途径（Bcl-2 和 Mcl-1）、外在途径（TRAIL 和 Fas）、p53 和内质网（ER）应激诱导的凋亡途径以及坏死性细胞死亡途径来控制程序性细胞死亡的调节剂。在这篇综述中，我们讨论了凋亡和坏死性细胞死亡途径的最新知识，以及这些途径在癌细胞中是如何受到损害的。我们重点讨论了 miRNAs 如何破坏细胞凋亡和坏死性细胞死亡，从而对恶性肿瘤的发生起到关键作用。了解哪些 miRNAs 及其靶基因影响细胞死亡途径，可能为癌症患者带来新的治疗机会。事实上，恢复促凋亡肿瘤抑制 miRNA（凋亡 miRNA）或抑制致癌 miRNA（癌 miRNA）是目前正在尝试的策略，或者已经作为 miRNA 为基础的癌症治疗方法应用。因此，更好地了解癌症类型特异性的凋亡 miRNA 和癌 miRNA 的表达及其在细胞死亡途径中的潜在机制，不仅将推进我们的知识，还将继续为癌症治疗提供新的机会。
