bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2025–06–29
six papers selected by
Muhammad Rizwan, COMSATS University



  1. World J Gastrointest Oncol. 2025 Jun 15. 17(6): 106161
       BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality globally. Exosomal microRNAs (miRNAs) are known to modulate tumor progression by influencing immune responses and vascular dynamics. However, the roles of specific exosomal miRNAs, such as miR-425-5p and miR-135b-3p, in CRC remain unclear.
    AIM: To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.
    METHODS: Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa. Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization, T cell differentiation, and vascular permeability assays, as well as in vivo tumor formation and metastasis experiments in nude mice. Validation experiments were performed using CRC cell lines (HCT116 and SW620).
    RESULTS: Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues. Functional studies revealed that miR-425-5p promotes macrophage M2-like polarization and suppresses T cell proinflammatory responses, while miR-135b-3p enhances vascular permeability and angiogenesis. Inhibition of these miRNAs in CRC cell-derived exosomes significantly suppressed tumor growth and metastasis in nude mice, reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune activation. Combined inhibition of both miRNAs resulted in the most pronounced effects.
    CONCLUSION: Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability. Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.
    Keywords:  Colorectal cancer; Exosomes; Immune modulation; MiR-135b-3p; MiR-425-5p; Vascular permeability
    DOI:  https://doi.org/10.4251/wjgo.v17.i6.106161
  2. Int J Mol Sci. 2025 Jun 06. pii: 5430. [Epub ahead of print]26(12):
      Breast cancer metastasis remains the primary driver of patient mortality, involving dynamic interactions between tumor cells and distant organ microenvironments. In recent years, tumor cell-derived extracellular vesicles (EVs) have emerged as critical information carriers, playing central roles in breast cancer metastasis by mediating organ-specific pre-metastatic niche formation, immune modulation, and tumor cell adaptive evolution. Studies have demonstrated that EVs drive the metastatic cascade through the delivery of bioactive components, including nucleic acids (e.g., miRNAs, circRNAs), proteins (e.g., integrins, metabolic enzymes), and lipids, which collectively regulate osteoclast activation, immune cell polarization, vascular permeability alterations, and extracellular matrix (ECM) remodeling in target organs such as bone, the lungs, and the liver. Molecular heterogeneity in EVs derived from different breast cancer subtypes strongly correlates with organotropism, providing potential biomarkers for metastasis prediction. Leveraging the organotrophic mechanisms of EVs and their dual regulatory roles in metastasis (pro-metastatic and anti-metastatic), strategies targeting EV biogenesis, cargo loading, or delivery exhibits translational potential in diagnostics and therapeutics. In this review, we summarize recent advances in understanding the role of breast cancer-derived exosomes in mediating metastatic organotropism and discuss the potential clinical applications of targeting exosomes as novel diagnostic and therapeutic strategies for breast cancer.
    Keywords:  breast cancer; breast cancer biomarkers; extracellular vesicles; metastasis
    DOI:  https://doi.org/10.3390/ijms26125430
  3. Int J Mol Sci. 2025 Jun 07. pii: 5483. [Epub ahead of print]26(12):
      This study explores the regulatory function of BAP31 on exosomal miRNA and its impact on the EMT in CRC. Exosomes from BAP31-OE cells promoted recipient cell migration and triggered the EMT, as indicated by decreased E-cadherin and increased N-cadherin and Vimentin levels. By contrast, exosomes derived from shBAP31 cells were observed to inhibit cell migration and revert EMT markers. The administration of shBAP31 exosomes significantly inhibited tumor growth in vivo. miRNA profiling revealed 76 differentially expressed miRNAs in BAP31-OE exosomes. Six miRNA candidates associated with the EMT were identified in the GEO database, miR-423-3p was identified as a key mediator, the candidates from shBAP31 exosomes exhibited the opposite effect. EMT promotion by miR-423-3p was further evidenced by EMT marker expression, enhanced migratory capacity, and accelerated tumor growth. Sixteen potential target genes were identified through bioinformatics analysis. Bim exhibited significant downregulation by the miR-423-3p mimic. Luciferase reporter assays verified the direct interaction between miR-423-3p and the 3'UTR of Bim. Silencing Bim negated the effects of miR-423-3p. It was also revealed that BAP31 does not influence the total exosomal miRNA content but selectively regulates miR-423-3p, which contains an EXOmotif enriched in BAP31-OE exosomes. Mechanistic studies revealed that BAP31 enhances the expression of the RNA export adaptor Alyref, as validated by qRT-PCR and Western blot analyses. RNA immunoprecipitation assays verified that Alyref binds to miR-423-3p in BAP31-OE cells. Our results reveal that BAP31 facilitates the sorting of exosomal miR-423-3p via Alyref, thereby promoting EMT in CRC through the miR-423-3p/Bim signaling axis. This indicates that BAP31 could be a viable therapeutic target for managing the EMT in CRC.
    Keywords:  Alyref; BAP31; Bim; EMT; exosomes; miR-423-3p
    DOI:  https://doi.org/10.3390/ijms26125483
  4. Front Oncol. 2025 ;15 1599608
      Lung cancer is the most prevalent and deadly malignant tumor in the world. Traditional treatment methods rely on histopathological analysis of cancer cells obtained through tissue biopsies, which carry risks due to their invasive nature. Thus, there is an urgent need to identify effective and non-invasive early screening methods for lung cancer. Exosomes, a crucial element of liquid biopsies, have emerged as a promising alternative due to their non-invasive collection, convenience and cost-effectiveness in diagnosing lung cancer. Research has underscored the role of exosomes in lung cancer invasion, metastasis, immune regulation, and the tumor microenvironment. Furthermore, the contents of exosomes, such as miRNAs, lncRNAs, circRNAs, and proteins, demonstrate considerable potential for the early diagnosis of lung cancer. This article provides a comprehensive review of the role and application of exosomes as liquid biopsy markers for early diagnosis of lung cancer, emphasizing their promise in improving patient outcomes through earlier detection and intervention.
    Keywords:  biomarkers; early diagnosis; exosomes; liquid biopsy; lung cancer
    DOI:  https://doi.org/10.3389/fonc.2025.1599608
  5. J Extracell Vesicles. 2025 Jun;14(6): e70091
      Advanced-stage prostate cancer (PCa) frequently causes bone metastases, resulting in a poor prognosis and a 5-year survival rate of 30%. PCa bone metastasis is a highly complex and fluctuating process, comprising of osteolytic (bone-degrading) and osteogenic (bone-forming) lesions. Although this system is mainly controlled by alterations in the receptor activator of NF-κB ligand (RANKL), RANKL-based treatment does not prolong the overall survival of patients with PCa bone metastasis. Therefore, it is essential to understand the other interactions between tumour cells and bone-resident cells in the metastatic niche to develop novel treatments. Extracellular vesicles (EVs) play key roles in intercellular communication and actively function in the bone microenvironment. We report that PCa cells corrupt osteoclasts (OCs) via their secretomes, inducing a pathological phenotype. EVs from pathological OCs activate bone-resorbing OCs and suppress bone-forming osteoblasts (OBs), leading to bone destruction. Pathological OCs increased IL-1β secretion and produced EVs with miR-5112 and miR-1963, targeting Parp1 in OCs and Hoxa1 in OBs. This led to OC maturation and IL-1β secretion, and inhibited OB mineralization. Injection of these miRNAs in vivo promoted PCa metastasis-disrupting bone. We report the mediation of EVs from OCs under pathological conditions that modulate the bone metastatic niche independently of RANKL.
    Keywords:  IL‐1β; bone metastasis; extracellular vesicles; osteoclast; prostate cancer
    DOI:  https://doi.org/10.1002/jev2.70091
  6. J Extracell Vesicles. 2025 Jun;14(6): e70089
      We explored the diagnostic utility of tumor-derived extracellular vesicles (tdEVs) in breast cancer (BC) by performing comprehensive proteomic profiling on plasma samples from 130 BC patients and 40 healthy controls (HC). Leveraging a microfluidic chip-based isolation technique optimized for low plasma volume and effective contaminant depletion, we achieved efficient enrichment of tdEVs. Proteomic analysis identified 26 candidate biomarkers differentially expressed between BC patients and HCs. To enhance biomarker selection robustness, we implemented a hybrid machine learning framework integrating LsBoost, convolutional neural networks, and support vector machines. Among the identified candidates, four EV proteins. ECM1, MBL2, BTD, and RAB5C. not only exhibited strong discriminatory performance, particularly for triple-negative breast cancer (TNBC), but also demonstrated potential relevance to disease recurrence, providing prognostic insights beyond initial diagnosis. Receiver operating characteristic (ROC) curve analysis demonstrated high diagnostic accuracy with an area under the curve (AUC) of 0.924 for BC and 0.973 for TNBC, as determined by mass spectrometry. These findings were further substantiated by immuno assay validation, which yielded an AUC of 0.986 for TNBC. Collectively, our results highlight the potential of EV proteomics as a minimally invasive, blood-based platform for both accurate detection and recurrence risk stratification in breast cancer and its aggressive subtypes, offering promising implications for future clinical applications.
    Keywords:  diagnosis; machine learning; microfluidics; proteomic analysis; triple‐negative breast cancer; tumour derived extracellular vesicles
    DOI:  https://doi.org/10.1002/jev2.70089