Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Immunol Cell Biol. 2021 Sep;99(8):814-832. doi: 10.1111/imcb.12477. Epub 2021 Jun 15.
The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single-stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune-related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.
哺乳动物雷帕霉素靶蛋白（mTOR）被认为是一种非典型的蛋白激酶，它在整合不同的细胞和环境输入方面起着关键作用，这些输入形式包括生长因子、营养物质和能量，随后调节不同的细胞事件，包括细胞代谢、存活、稳态、生长和细胞分化。在免疫学方面，mTOR 通过整合来自免疫微环境的众多信号，是免疫功能的关键调节剂，协调免疫细胞的功能和 T 细胞命运决定。mTOR 在免疫反应中的关键作用最近得到了更多的重视。微小 RNA（miRNA）是内源性的、小的、非编码的单链 RNA，作为分子调节剂参与免疫细胞发育、稳态、激活和效应极化过程中的多种过程。最近的几项研究表明，一系列 miRNA 通过靶向该信号通路的多个成分并调节这些靶标的表达和功能，参与调节磷酸肌醇 3-激酶/蛋白激酶 B/mTOR（PI3K/AKT/mTOR）信号通路。目前的证据揭示了 miRNA 和 mTOR 通路在各种免疫细胞类型中的相互作用。单个 miRNA 的表达可以通过协调免疫信号和细胞代谢来影响 mTOR 信号的功能，从而决定免疫反应中的细胞命运决定。mTOR 通路/miRNA 串扰的失调已在癌症和各种免疫相关疾病中报道。因此，失调 miRNA 的表达谱可能会影响 mTOR 通路，导致异常免疫的促进。这篇综述总结了关于 mTOR 信号通路和 miRNA 在协调免疫反应中的相互作用的最新信息。
