Exosome-derived circUPF2 enhances resistance to targeted therapy by redeploying ferroptosis sensitivity in hepatocellular carcinoma

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 30, 2024

Abstract Background Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, effectiveness of sorafenib greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in cancer’s malignant advancement. However, significance exosomal development resistance HCC remains uncertain. Methods Ultracentrifugation was utilized isolate (Exo-SR) from sorafenib-resistant cells’ culture medium. Transcriptome sequencing differential expression gene analysis were used identify targets Exo-SR action cells. To cells, transcriptome genes employed. evaluate impact circUPF2 on HCC, experiments involving gain-of-function loss-of-function conducted. RNA pull-down assays mass spectrometry performed RNA-binding proteins interacting circUPF2. immunoprecipitation (RIP), pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence situ hybridization (FISH), rescue validate interactions among circUPF2, IGF2BP2 SLC7A11. Finally, tumor xenograft examine biological functions underlying mechanisms vivo. Results A novel circRNA, identified revealed significantly enriched Exo-SR. Exosomes enhanced by promoting SLC7A11 suppressing ferroptosis Mechanistically, acts as framework enhance creation circUPF2-IGF2BP2-SLC7A11 ternary complex contributing stabilization mRNA. Consequently, promotes enhances function system Xc- leading decreased sensitivity sorafenib. Conclusions The facilitated formation increases stability Focusing could potentially an innovative approach treatment. Graphical

Language: Английский

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Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 3, 2024

Extracellular vesicles (EVs) have been proven to play a significant immunoregulatory role in many chronic diseases, such as cancer and immune disorders. Among them, EVs derived from NK cells are an essential component of the cell functions. These demonstrated carry variety toxic proteins nucleic acids therapeutic diseases like malignancies, liver fibrosis, lung injury. However, natural NK-derived (NKEVs) certain limitations disease treatment, low yield poor targeting. Concurrently, exhibit characteristics memory-like cells, which stronger proliferative capacity, increased IFN-γ production, enhanced cytotoxicity, making them more advantageous for treatment. Recent research has shifted its focus towards engineered extracellular their potential improve efficiency, specificity, safety treatments. In this review, we will discuss latest advancements therapy. Specifically, compare different cellular sources NKEVs explore current status prospects cell-derived NKEVs.

Language: Английский

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Advanced approaches of the use of circRNAs as a replacement for cancer therapy

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(3), P. 811 - 830

Published: March 30, 2024

Cancer is a broad name for group of diseases in which abnormal cells grow out control and are characterized by their complexity recurrence. Although there has been progress cancer therapy with the entry precision medicine immunotherapy, incidence rates have increased globally. Non-coding RNAs form circular (circRNAs) play crucial roles pathogenesis, clinical diagnosis, different diseases, including cancer. According to recent studies, circRNAs appear serve as accurate indicators therapeutic targets treatment. However, promising candidates cutting-edge because distinctive structure, stability, wide range capabilities; many challenges persist that decrease applications circRNA-based therapeutics. Here, we explore replacement therapy, highlight main facing therapies, discuss key strategies overcome these improve advanced innovative therapies based on long-term health effects.

Language: Английский

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Engineering Exosomes for Therapeutic Applications: Decoding Biogenesis, Content Modification, and Cargo Loading Strategies

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 7137 - 7164

Published: July 1, 2024

Abstract: Exosomes emerge from endosomal invagination and range in size 30 to 200 nm. contain diverse proteins, lipids, nucleic acids, which can indicate the state of various physiological pathological processes. Studies have revealed remarkable clinical potential exosomes diagnosing prognosing multiple diseases, including cancer, cardiovascular disorders, neurodegenerative conditions. also be engineered deliver their cargo a specific target. However, further advancements are imperative optimize exosomes' diagnostic therapeutic capabilities for practical implementation settings. This review highlights applications, emphasizing engineering through simple incubation, biological, click chemistry techniques. Additionally, loading agents onto exosomes, utilizing passive active strategies, exploring hybrid artificial discussed. Keywords: exosome, drug delivery, diagnostics, therapeutics

Language: Английский

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Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 24, 2024

Abstract The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that obesity, matrix protein 1 (ECM1) levels are significantly increased circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 but reduces the sEVs released by these cells. In breast cancer (BC), overexpressing increases metalloproteinase 3 (MMP3) and S100A/B levels. Interestingly, purified from high-fat diet-induced obesity mice (D-sEVs) deliver more to BC cells compared control diet-fed mice. Consequently, secrete protein, promotes cell invasion migration. D-sEVs treatment also enhances ECM1-mediated metastasis growth mouse models, as evidenced elevated tumor MMP3 S100A/B. study reveals a mechanism suggests sEV-based strategies for treating obesity-associated BC.

Language: Английский

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Exosomal lncRNAs as diagnostic and therapeutic targets in multiple myeloma

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 16, 2025

Multiple Myeloma (MM) is the second most common malignancy of hematopoietic system, accounting for approximately 10% all hematological malignancies, and currently, there no complete cure. Existing research indicates that exosomal long non-coding RNAs (lncRNAs) play a crucial regulatory role in initiation progression tumors, involving various interactions such as lncRNA-miRNA, lncRNA-mRNA, lncRNA-RNA binding proteins (RBP). Despite significant clinical application potential lncRNAs, this area still faces challenges due to their low abundance technical limitations. To our knowledge, review first comprehensively integrate elucidate three mechanisms action lncRNAs MM, propose therapeutic targets cases based on these mechanisms. We highlight latest advancements biomarkers targets, offering not only comprehensive analysis MM but also new perspectives methods future diagnosis treatment multiple myeloma.

Language: Английский

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Exosomes in oral squamous cell carcinoma: functions, challenges, and potential applications

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 16, 2025

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of all oral cancers, significantly impacting the survival and quality life patients. Exosomes, small extracellular vesicles released by cells, play a crucial role in intercellular communication cancer. Nevertheless, their function mechanism OSCC remain elusive. Search Pubmed, Web Science, Cochrane Library using keywords OSCC, exome, diagnosis, treatment to review research progress exome OSCC. Based on these results, this starting from biosynthesis, structure, contents exosomes, elaborates exosomes diagnosis It explores potential briefly describes challenges researchers currently face.

Language: Английский

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Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010928 - e010928

Published: March 1, 2025

Immunotherapy of cancer is now an essential pillar treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration new strategies incorporating agents in clinical practice. Immunotherapies perturb complex system interactions among genomically unstable cells, diverse cells within the microenvironment including systemic adaptive innate cells. The drive to develop increasingly effective immunotherapy regimens tempered by risk immune-related adverse events. Evidence-based biomarkers that measure potential therapeutic response and/or toxicity critical guide optimal patient care contextualize results trials. Responding lack guidance on biomarker testing early-phase trials, we propose definition listing recommended inclusion all such protocols. These recommendations based consensus provided Society Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty input from SITC Pathology Biomarker Committees Journal ImmunoTherapy readership. A consensus-based selection was conducted using Delphi survey SCION faculty. Regular updates these planned. inaugural list includes complete blood count differential generate neutrophil-to-lymphocyte ratio or immune-inflammation index, serum lactate dehydrogenase albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, mutational burden. Inclusion across trials will capture variation provide deeper insight into novel established therapies, support improved stratification later-phase

Language: Английский

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Fibrinogen-like 2 in tumor-associated macrophage-derived extracellular vesicles shapes an immunosuppressive microenvironment in colorectal liver metastases by promoting tumor stemness and neutrophil extracellular traps formation

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217642 - 217642

Published: March 1, 2025

Language: Английский

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Precise Identification and Profiling of Surface Proteins of Ultra Rare Tumor Specific Extracellular Vesicle with Dynamic Quantitative Plasmonic Imaging

ACS Nano, Journal Year: 2023, Volume and Issue: 17(17), P. 16656 - 16667

Published: Aug. 28, 2023

Specific detection of tumor-derived EVs (tEVs) in plasma is complicated by nontumor and non-EV particles. To accurately identify tEVs profile their surface protein expression at single tEV resolution directly with clinical still an unmet need. Here, we present a Dynamic Immunoassay for Single Profiling (DISEP), kinetic assay based on plasmon resonance microscopy (SPRM) specific profiling. DISEP adopts pair low-affinity oligonucleotide probes to respectively label EV proteins functionalize SPRM biosensor interface. labeled the possess distinctive binding kinetics from nonspecific particles plasma, which permits accurate digital plasmonic counting EVs. We demonstrate recognizing target among 350-fold background high sensitivity (4677 per μL). Clinical samples were analyzed discriminate between pancreatic cancer patients (n = 40) healthy donors 45). With panel biomarker signatures (EpCAM, HER2, GPC1), only requires 10 μL primary sample each donor classify tumor area under curve 0.98. provides highly profiling strategy early diagnosis.

Language: Английский

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