Circular RNAs (circRNAs) are stable RNAs present in cell-free RNA, which may comprise cellular debris and pathogen genomes. Here, we investigate the phenomenon and mechanism of cellular uptake and intracellular fate of exogenous circRNAs. Human myeloid cells and B cells selectively internalize extracellular circRNAs. Macrophage uptake of circRNA is rapid, energy dependent, and saturable. CircRNA uptake can lead to translation of encoded sequences and antigen presentation. The route of internalization influences immune activation after circRNA uptake, with distinct gene expression programs depending on the route of RNA delivery. Genome-scale CRISPR screens and chemical inhibitor studies nominate macrophage scavenger receptor MSR1, Toll-like receptors, and mTOR signaling as key regulators of receptor-mediated phagocytosis of circRNAs, a dominant pathway to internalize circRNAs in parallel to macropinocytosis. These results suggest that cell-free circRNA serves as an "eat me" signal and danger-associated molecular pattern, indicating orderly pathways of recognition and disposal.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218042 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2024.04.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation.
Mol Cancer
January 2025
Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China.
Background: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC), faces resistance issues, partly due to myeloid-derived suppressor cells (MDSCs) that enhance immunosuppression in the tumor microenvironment (TME).
Methods: Various murine HCC cell lines and MDSCs were used in a series of in vitro and in vivo experiments. These included subcutaneous tumor models, cell viability assays, flow cytometry, immunohistochemistry, and RNA sequencing.
FlashTag-mediated Labeling for Intraventricular Macrophages in the Embryonic Brain.
Bio Protoc
January 2025
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
The fate mapping technique is essential for understanding how cells differentiate and organize into complex structures. Various methods are used in fate mapping, including dye injections, genetic labeling (e.g.
View Article and Find Full Text PDFMetal-Phenolic Nanomedicines Targeting Fatty Acid Metabolic Reprogramming to Overcome Immunosuppression in Radiometabolic Cancer Therapy.
ACS Appl Mater Interfaces
January 2025
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
Radiation therapy (RT) is a prevalent cancer treatment; however, its therapeutic outcomes are frequently impeded by tumor radioresistance, largely attributed to metabolic reprogramming characterized by increased fatty acid uptake and oxidation. To overcome this limitation, we developed polyphenol-metal coordination polymer (PPWQ), a novel nanoradiotherapy sensitizer specifically designed to regulate fatty acid metabolism and improve RT efficacy. These nanoparticles (NPs) utilize a metal-phenolic network (MPN) to integrate tungsten ions (W), quercetin (QR), and a PD-L1-blocking peptide within a PEG-polyphenol scaffold.
View Article and Find Full Text PDFAssessing the impact of TiO nanomaterials on intestinal cells: new evidence for epithelial translocation and potential pro-inflammatory effects.
Toxicology
January 2025
National Institute of Health Doutor Ricardo Jorge, I.P (INSA), Department of Human Genetics, Lisbon, Portugal; (b)Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address:
Understanding the potential impact of nanomaterials (NMs) on human health requires further investigation into the organ-specific nano-bio interplay at the cellular and molecular levels. We showed increased chromosomal damage in intestinal cells exposed to some of in vitro digested Titanium dioxide (TiO) NMs. The present study aimed to explore possible mechanisms linked to the uptake, epithelial barrier integrity, cellular trafficking, as well as activation of pro-inflammatory pathways, after exposure to three TiO-NMs (NM-102, NM-103, and NM-105).
View Article and Find Full Text PDFKnock-out mouse models and single particle ICP-MS reveal that SP-D and SP-A deficiency reduces agglomeration of inhaled gold nanoparticles in vivo without significant changes to overall lung clearance.
Nanotoxicology
January 2025
Infection, Inflammation and Repair, Faculty of Medicine, University of Southampton, Southampton, UK.
The role of surfactant proteins A and D (SP-A and SP-D) in lung clearance and translocation to secondary organs of inhaled nanoparticles was investigated by exposing SP-A and SP-D knockout (AKO and DKO) and wild type (WT) mice nose-only for 3 hours to an aerosol of 20 nm gold nanoparticles (AuNPs). Animals were euthanised at 0-, 1-, 7- and 28-days post-exposure. Analysis by inductively coupled plasma mass spectrometry (ICP-MS) of the liver and kidneys showed that extrapulmonary translocation was below the limits of detection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!