Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

Sapoń

2020

IJMS

Intraluminal vesicles (ILVs) are released into the extracellular space as exosomes after the fusion of multivesicular bodies (MVBs) with the plasma membrane. miRNAs are delivered to the raft-like region of MVB by RNA-binding proteins (RBPs). RNA loading into exosomes can be either through direct interaction between RNA and the raft-like region of the MVB membrane, or through interaction between an RBP–RNA complex with this raft-like region. Selection of RNA aptamers that bind to lipid raft region of liposomal membranes was performed using the selection-amplification (SELEX) method. The pool of RNA aptamers was isolated, and the binding of this pool to lipid-raft regions was demonstrated. Sequencing of clones from rafted liposome-eluted RNAs showed sequences apparently of independent origin. Bioinformatics analysis revealed the most frequent raft-motifs present within these sequences. Four raft RNA motifs, one of them an EXO motif, have been identified. These motifs appear to be most frequent both in the case of raft RNA aptamers and in the case of exosomal pro-tumoral miRNAs transferred from cancer cells to macrophages, natural killer cells and dendritic cells, thus suggesting that the selection for incorporation of these miRNAs into ILVs is based on their affinity to the raft-like region of the MVB membrane.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Binding of RNA Aptamers to Membrane Lipid Rafts: Implications for Exosomal miRNAs Transfer from Cancer to Immune Cells

Sapoń

2020

IJMS

“…Vesicles with exosome-like structures were discovered by (38), while the true definition of exosomes was in 1983 (39). During the past decade, with the in-depth study of exosomes, it has been found that exosomes are involved in the development and prognosis of various diseases (40)(41)(42)(43)(44), and especially, play an irreplaceable role in tumor invasion (45), metastasis (46), and progression (47). Exosomes contain a variety of bioactive molecules, including proteins, RNAs, cholesterol, and lipids (24,(48)(49)(50)(51)(52).…”

Section: Exosome Biology and Functionmentioning

confidence: 99%

Exosome-Derived LncRNAs in Lung Cancer

Fan

Sun

2020

Front. Oncol.

As extracellular vesicles, exosomes are released from most cells to perform cell-cell communication. Recent studies have shown that exosomes could be released into tumor microenvironment and blood to promote tumor progression through packaging and transmitting various bioactive molecules, such as cholesterol, proteins, lipids, miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to distant cells. LncRNAs have emerged as a major class of non-coding transcripts. A lot of LncRNAs have been discovered during the past few years of research on genomics. They have been proven to participate in various biological functions and disease processes through multiple mechanisms. In this review, we analyzed the role of exosome-derived lncRNAs in lung carcinogenesis and metastasis. We also highlight opportunities for the clinical potential of exosomes with specific lncRNAs as biomarkers and therapeutic intervention in lung cancer.

“…It has been demonstrated that some miRNAs interact with long non-coding RNAs (lncRNAs) [ 5 , 6 ] and can degrade them directly, thus interfering with lncRNA functionality. Further studies have suggested that the aberrant expression of miRNAs is associated with many human diseases; owing to their secretion into extracellular fluids, miRNAs are considered as potential biomarkers [ 7 , 8 , 9 , 10 , 11 , 12 ]. Some miRNAs are incorporated into exosomes, where they serve as signaling inducers to regulate cell–cell communication and bystander cell function [ 10 , 12 , 13 , 14 ] and some of them are reported to possess the ability to bind to viral RNAs and exert direct antiviral properties [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Profiles in Monocyte-Derived Macrophages Generated by Interleukin-27 and Human Serum: Identification of a Novel HIV-Inhibiting and Autophagy-Inducing MicroRNA

Imamichi

Goswami

et al. 2021

IJMS

Interleukin-27 (IL-27) is a pleiotropic cytokine that influences the innate and adaptive immune systems. It inhibits viral infection and regulates the expression of microRNAs (miRNAs). We recently reported that macrophages differentiated from human primary monocytes in the presence of IL-27 and human AB serum resisted human immunodeficiency virus (HIV) infection and showed significant autophagy induction. In the current study, the miRNA profiles in these cells were investigated, especially focusing on the identification of novel miRNAs regulated by IL-27-treatment. The miRNA sequencing analysis detected 38 novel miRNAs. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed that IL-27 differentially regulated the expression of 16 of the 38 miRNAs. Overexpression of the synthesized miRNA mimics by transfection revealed that miRAB40 had potent HIV-inhibiting and autophagy-inducing properties. B18R, an interferon (IFN)-neutralization protein, partially suppressed both activities, indicating that the two functions were induced via IFN-dependent and -independent pathways. Although the target mRNA(s) of miRAB40 involving in the induction of both functions was unable to identify in this study, the discovery of miRAB40, a potential HIV-inhibiting and autophagy inducing miRNA, may provide novel insights into the miRNA (small none-coding RNA)-mediated regulation of HIV inhibition and autophagy induction as an innate immune response.