The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses

Abstract

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.

Identifying novel SMYD3 interactors on the trail of cancer hallmarks

“…mTOR signaling is a key regulator of immune cell metabolism and function. It acts as a part of two structurally and functionally distinct signaling complexes, mTORC1 and mTORC2 (mTOR complexes 1 and 2) [55] . mTORC2 signaling is required for the generation of M2 macrophages [56] .…”

mTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment

“…Hypoxiainduced tumor exosomes containing let-7a microRNA (miRNA) enhance mitochondrial OXPHOS activity and suppress insulin/Akt/ mTOR signaling pathway in bone marrow-derived macrophages (BMMs), as a result, promotes polarization of infiltrating macrophages to an M2-like phenotype. Therefore, biomoleculeloaded exosomes, such as let-7a, enhance tumor immune evasion and tumor progression by promoting changes in immunometabolic profile of infiltrating monocyte-macrophage population (Figure 3) (2,142). miR-100 is highly expressed in TAMs and promotes M2polarization of macrophages, and maintains TAMs phenotype through the downregulation of the mTOR signaling pathway.…”

“…The mammalian target of rapamycin (mTOR; now officially known as the mechanistic target of rapamycin) is a ubiquitous serine/threonine-specific protein kinase, plays a critical role in regulating numerous cellular functions, including cell growth, proliferation, survival, protein synthesis, ribosome biogenesis, autophagy, and metabolism (1,2). mTOR functions within two functionally and structurally distinct multi-component kinase complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) that act as the central nodes of the phosphoinositide 3-kinase (PI3K)/Akt downstream signaling pathway (3).…”

Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma

“…Recent studies reported that mTOR could regulate tumor immunity through modulating the interactions between the stroma and the tumor, thus possibly promote carcinogenesis (Guri, Nordmann & Roszik, 2018;Irelli et al, 2019). mTOR not only regulated the innate and adaptive immune response through modulating the effector response of innate immune cells such as macrophage, DCs, neutrophils and NKs, but also played a prerequisite role in the development of adaptive immune cells, such as CD4+ T, CD8+ T, Tregs and B cells (Nazari et al, 2021). The underlying mechanism behind the association of mTOR expression and immune cells has not been clearly illustrated.…”