Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 6, 2025

Drug resistance and immune escape continue to contribute poor prognosis in AML. Increasing evidence suggests that exosomes play a crucial role AML microenvironment. Sanger sequencing, RNase R fluorescence situ hybridization were performed confirm the existence of circ_0006896. The circ_0006896 progression was assessed by vitro vivo functional experiments. Flow cytometry, RT-qPCR adoptive T cell-transfer immunotherapy conducted assess function exosomal CD8+ cell dysfunction. RNA pull-down assay, mass spectrometry, immunofluorescence, co-immunoprecipitation western blot identify interacting proteins. CircRNA expression patterns differ significantly between controls compared lncRNAs or mRNAs. A new circRNA, circ_0006896, is upregulated both cells correlates with relapse In studies suggest promotes proliferation, reduces chemotherapy sensitivity, more importantly, impairs efficacy immunotherapy. Mechanistically, physically interacts catalytic domain histone deacetylase HDAC1, decreasing H3 acetylation, impairing transcription genes involved arachidonic acid metabolism, ultimately inhibiting lipid peroxidation ferroptosis cells. Exosomal disrupts LEF1 subsequently cytotoxic molecules IFN-γ Granzyme B. We demonstrate self-driven mediated circRNAs cells, highlighting potential targeting

Language: Английский

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Therapeutic potential: The role of mesenchymal stem cells from diverse sources and their derived exosomes in diabetic nephropathy

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116672 - 116672

Published: April 26, 2024

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients, with its incidence continuously increasing recent years. DN causes renal tissue damage and functional decline, expedites aging process kidneys, may ultimately progress leading to end-stage disease, severely impacting patient's quality life prognosis. Mesenchymal stem cells (MSCs) are highly valued for their multipotent differentiation, paracrine functions, immunomodulatory effects, capacity repair. Particularly, exosomes (Exo) derived from MSCs (MSCs-Exo) rich bioactive molecules facilitate intercellular communication, participating various physiological pathological processes. MSCs-Exo, particular, have been demonstrated therapeutic effects treatment research by encouraging repair, fibrosis inhibition, inflammation reduction. Research has shown that MSCs-Exo promoting inhibiting fibrosis, reducing inflammation. Recent studies underscore potential highlighting broad applicability treatment. This review aims provide a comprehensive summary scientific developments treating using diverse sources, while also exploring future possibilities detail.

Language: Английский

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Acute Myeloid Leukemia Cells Educate Mesenchymal Stromal Cells toward an Adipogenic Differentiation Propensity with Leukemia Promotion Capabilities

Advanced Science, Journal Year: 2022, Volume and Issue: 9(16)

Published: March 20, 2022

Mesenchymal stromal cells (MSCs) are essential elements of the bone marrow (BM) microenvironment, which have been widely implicated in pathways that contribute to leukemia growth and resistance. Recent reports showed genotypic phenotypic alterations patient-derived MSCs, indicating MSCs might be educated/reprogrammed. However, results inconclusive, possibly due heterogeneity leukemia. Here, authors report acute myeloid (AML) induces towards an adipogenic differentiation propensity. RNAseq analysis reveal significant upregulation gene expression enriched adipocyte process reduction osteoblast differentiation. The alteration is accompanied by a metabolic switch from glycolysis more oxidative phosphorylation-dependent manner. Mechanistic studies identify AML cell-derived exosomes play vital role during cell-mediated education/reprogramming process. Pre-administration mice BM microenvironment with AML-derived greatly enhance engraftment vivo. quantitative proteomic identified list exosomal protein components differently expressed exosomes, represent opportunity for novel therapeutic strategies based on targeting exosome-based cells-MSCs communication. Collectively, data show AML-educated tend differentiate into adipocytes contributing disease progression, suggests complex interactions components.

Language: Английский

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Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4430 - 4430

Published: April 17, 2024

Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed treatment-resistant leukaemic stem cells (LSCs) residing bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role extracellular vesicles (EVs) dynamic remodelling BM niche intercellular communication. We explore recent advancements elucidating mechanisms through which EVs facilitate complex crosstalk, effectively promoting hallmarks drug resistance. Adopting temporal view, we chart evolving landscape EV-mediated interactions within niche, underscoring transformative potential these insights for therapeutic intervention. Furthermore, discusses emerging understanding endothelial cell subsets' impact across niches shaping disease adding another layer complexity progression treatment highlight cutting-edge methodologies, such as organ-on-chip (OoC) single-EV technologies, provide unprecedented into AML-niche human setting. Leveraging accumulated EV signalling reconfigure pioneer novel approaches decipher networks that fuel context could revolutionise development niche-targeted therapy eradication.

Language: Английский

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Non-Classical Intercellular Communications: Basic Mechanisms and Roles in Biology and Medicine

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6455 - 6455

Published: March 29, 2023

In multicellular organisms, interactions between cells and intercellular communications form the very basis of organism's survival, functioning its systems, maintenance homeostasis adequate response to environment. The accumulated experimental data point particular importance in determining fate cells, as well their differentiation plasticity. For a long time, it was believed that properties behavior were primarily governed by secreted or membrane-bound ligands with corresponding receptors, direct adhesion contacts. this review, we describe various types other, non-classical have recently come into limelight-in particular, broad repertoire extracellular vesicles membrane protrusions. These are mediated large macromolecular structural functional ensembles, explore here mechanisms underlying formation present current reveal roles multiple biological processes. effects these new normal pathological states, therapeutic applications, also discussed. in-depth study novel interaction is required for establishment effective approaches control modification cell both basic research development radically strategies.

Language: Английский

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Gastric cancer derived mesenchymal stem cells promoted DNA repair and cisplatin resistance through up-regulating PD-L1/Rad51 in gastric cancer

Cellular Signalling, Journal Year: 2023, Volume and Issue: 106, P. 110639 - 110639

Published: Feb. 25, 2023

Language: Английский

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Y‐box binding protein 1 in small extracellular vesicles reduces mesenchymal stem cell differentiation to osteoblasts—implications for acute myeloid leukaemia

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(3)

Published: March 1, 2024

Abstract Small extracellular vesicles (sEVs) released by acute myeloid leukaemia (AML) cells have been reported to influence the trilineage differentiation of bone marrow‐derived mesenchymal stem (BM‐MSCs). However, it remains elusive which biological cargo from AML‐sEVs is responsible for this effect. In study, sEVs were isolated cell‐conditioned media and blood plasma using size‐exclusion chromatography ultrafiltration characterized according MISEV2018 guidelines. Our results demonstrated that increased proliferation BM‐MSCs. Conversely, key proteins are important normal haematopoiesis downregulated in Additionally, we revealed significantly reduced BM‐MSCs osteoblasts without affecting adipogenic or chondrogenic differentiation. Next, LC‐MS/MS proteomics elucidated various proteins, including Y‐box‐binding protein 1 (YBX1), upregulated both treated with AML‐sEVs. Clinically relevant, found YBX1 considerably most paediatric AML patient‐derived compared healthy controls. Interestingly, after downregulation remarkably rescued osteoblastic Altogether, our data demonstrate first time containing one players disrupt function marrow microenvironment reducing osteogenic

Language: Английский

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Drug Resistance: The Role of Exosomal miRNA in the Microenvironment of Hematopoietic Tumors

Molecules, Journal Year: 2022, Volume and Issue: 28(1), P. 116 - 116

Published: Dec. 23, 2022

Extracellular vesicles (EVs), including exosomes, have an important role thanks to their ability communicate and exchange information between tumor cells the microenvironment (TME), also been associated with communicating anti-cancer drug resistance (DR). The increase in proliferation of cancer alters oxygen levels, which causes hypoxia results a release exosomes by cells. In this review, studies examining exosomal miRNA DR, mechanism, are discussed detail hematological tumors: leukemia, lymphoma, multiple myeloma. conclusion, we underline exosome’s function as possible delivery vehicle understanding its cargo. Engineered can be used more specific for personalized therapy.

Language: Английский

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Hydrogels Empowered Mesenchymal Stem Cells and the Derived Exosomes for Regenerative Medicine in Age-Related Musculoskeletal Diseases

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107618 - 107618

Published: Jan. 1, 2025

Language: Английский

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Extracellular vesicles secreted by leukemic cells as mediators of dysregulated hematopoiesis: acute myeloid leukemia as a case in point

Expert Review of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Acute myeloid leukemia (AML) cells exhibit a profound capacity for resistance to conventional chemotherapeutic agents, posing substantial challenge existing therapeutic paradigms. Interestingly, this happens in the face of luxuriant proliferation leukemic blasts peripheral blood. This paradox concurrent proliferative activity and cellular quiescence underscores complex biological phenomenon that is intricately mediated by AML-derived Extracellular vesicles (EVs). An extensive literature review search was done on Pubmed/Scopus/Web Sciences databases identify studies published between 2013 2024 elucidating demonstrating effect EVs, Microvesicles (MVs) Exosomes (Exos) regulating normal dysregulated bone marrow (BM) niche. The delves into understanding molecular mechanisms underlying dual behavior AML - quiescence, with special focus role EVs their subtypes viz. Exos MVs establishing discrete BM microenvironment subversive chemotherapy. It offers novel perspective intricate interplay microenvironment, implications interventions targeting persistence drug resistance.

Language: Английский

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