Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes

We report the separation of two small EV sub-populations from a metastatic breast cancer cell line, with biochemical features consistent with different sub-cellular origins. These EV sub-types use different mechanisms of miRNA sorting (selective and non-selective), suggesting that sorting occurs via fundamentally distinct processes, possibly dependent on EV origin. Using biochemical and genetic tools, we identified the Lupus La protein as mediating sorting of selectively packaged miRNAs. We found that two motifs embedded in miR-122 are responsible for high-affinity binding to Lupus La and sorting into vesicles formed in a cell-free reaction. Thus, tumor cells can simultaneously deploy multiple EV species using distinct sorting mechanisms that may enable diverse functions in normal and cancer biology.
Source: eLife - Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cancer Biology Source Type: research

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Authors: Tattevin P, Tchamgoué S, Belem A, Bénézit F, Pronier C, Revest M Abstract Aseptic meningitis is defined as meningeal inflammation - i.e. cerebrospinal fluid (CSF) pleocytosis≥5 cells/mm3 - not related to an infectious process. Etiologies of aseptic meningitis can be classified in three main groups: (i) systemic diseases with meningeal involvement, which include sarcoidosis, Behçet's disease, Sjögren's syndrome, systemic lupus erythematosus and granulomatosis with polyangiitis; (ii) drug-induced aseptic meningitis, mostly reported with non-steroidal an...
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research
Abstract Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial signal from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and my...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Br J Clin Pharmacol Source Type: research
Purpose: To evaluate the infection incidence in breast cancer patients whether they have a major autoimmune disease or not.Methods: This retrospective cohort study compared the infection incidence of 174 breast cancer patients with an autoimmune disease, including Sjogren's Syndrome (SS), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE), along with 4429 patients without an autoimmune disease, for the period 2000 to 2016. Six-hundred and ninety six, age-, stage-, and diagnosis era-matched patients without any autoimmune disease were analyzed to eliminate the effects of these confounding factors may have on ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion The elucidation of the function of circRNAs is an emerging field of science with a tremendous potential after previously being dismissed as RNA artifacts. They are ubiquitously expressed and thousands of members have already been identified. This fact only expands their potential to possibly enhance our knowledge to understand the difference between health and disease. Owing to their structure stability and their presence in exosomes circRNAs may also exert their function in an autocrine, paracrine and possible endocrine fashion. In addition, the fact that circRNAs are widely distributed in the cellular compart...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Perspectives Being exquisitely regulated by “writers,” “erasers,” and “readers,” additional repelled proteins or miRNAs, m6A modification relates to nearly any step of mRNA metabolism, as well as ncRNA processing and circRNA translation. There is compelling evidence suggesting that m6A modification is especially critical in a variety of pathologic and physiologic immune responses including T cell homeostasis and differentiation, inflammation, and type I interferon production. Further results have indicated that aberrancies of interferon and Th17 frequencies in systemic lu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we firstly tested the effects of QJSB on leucopenia using mice induced by cyclophosphamide. Our results suggested that QJSB significantly raised the number of peripheral white blood cells, platelets and nucleated bone marrow cells. Additionally, it markedly enhanced the cell viability and promoted the colony formation of bone marrow mononuclear cells. Furthermore, it reversed the serum cytokines IL-6 and G-CSF disorders. Then, using transcriptomics datasets and metabonomic datasets, we integrated transcriptomics-based network pharmacology and metabolomics technologies to investigate the mechanism of action o...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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