bims-exocan 2025-10-19 papers

Issue of 2025–10–19
six papers selected by
Muhammad Rizwan, COMSATS University

Curr Mol Med. 2025 Oct 10.

Roles of Exosomes in Cancer Pathogenesis, Progression, and Therapy Resistance.

Zinnat Ara Moni, Tasnima Kamal, Abdul Auwal, M Matakabbir Hossain, Md Imtiaj Ahmad Bulbul, Nitai Roy, Farhadul Islam.

Cancer is a major health concern worldwide, and there have been numerous efforts to fully understand the mechanism of cancer pathogenesis and develop effective treatments. In this context, exosomes play a crucial role in the detection and management of cancer. Exosomes are extracellular vesicles that share components with their parent cells and mediate intercellular communication, especially in cancer patients. Exosomal cargo, which includes proteins, lipids, and RNAs, has been extensively investigated due to its potential significance in cancer. Exosomes play a crucial role in cancer biology, as they have been demonstrated to alter the tumor microenvironment and facilitate communication between the tumor and its host. Exosomal composition is influenced by packaging and secretion processes, which can affect the function, distribution, and uptake of cargo in target cells. Exosome-mediated communication within the tumor microenvironment suggests that variations in endocytosis and plasma membrane remodeling, which are specific to cancer, are partly responsible for the abnormal exosomal process in cancer. Numerous processes, including the modification of the tumor microenvironment, the promotion of angiogenesis, metastasis, and invasion, as well as the regulation of tumor cells' immune escape, are thought to be facilitated by exosomes in the development and progression of cancers originating from various tissues. Exosomal components have the ability to mediate immune responses against cancer and aid in the development of cancer cell resistance to treatments and medications. This study aims to provide a concise review of exosome composition, the processes involved in their synthesis, their roles in cancer development, progression, and metastasis, as well as their ability to evade immune surveillance and contribute to resistance against cancer-related drugs and therapies. Therefore, we conducted an extensive search across numerous academic databases, including Scopus, PubMed, ScienceDirect, Crossref, and Google Scholar, using the keywords "cancer," "exosomes," "progression," "metastasis," "therapy resistance," etc. The retrieved literature was critically analyzed. This knowledge may contribute to more effective cancer treatment in the future by informing potential therapeutic applications.

Keywords: Exosomes; biogenesis; metastasis; progression; therapy resistance.; tumorigenesis

DOI: https://doi.org/10.2174/0115665240374643250902181706

Molecules. 2025 Sep 23. pii: 3858. [Epub ahead of print]30(19):

Exosomal MicroRNA: Diagnostic Potential and Role in Breast Cancer Dissemination.

Svetlana Tamkovich, Alexandra Borisova, Andrey Shevela, Alexander Chernyavskiy, Alyona Chernyshovа.

Liquid biopsy, which analyzes tumor secretomes in biological fluids, allows us to not only diagnose cancer, but also evaluate the effectiveness of antitumor therapy, predict the prognosis of the disease, and select targeted therapy. One of the promising sources for identifying tumor markers using liquid biopsy is exosomes-small extracellular vesicles (sEVs) (30-150 nm in size) that are secreted by all types of cells, including tumor cells, to exchange information. It is known that during the maturation process, mainly biologically active proteins and non-coding RNA are packaged into exosomes, and tumor cells secrete significantly more exosomes than normal cells. Taking into account the involvement of microRNAs in the mechanisms of carcinogenesis, their high stability in EVs, and ease of detection, exosomal microRNAs are the most promising tumor markers for creating panels that can serve as a guide both for clarifying diagnostics and for making therapeutic decisions on effective cancer treatment, including breast cancer (BC). The purpose of this review is to summarize information on the shortcomings of modern methods for diagnosing early BC, the involvement of exosomal microRNAs in BC dissemination (impact on the immune system, epithelial-mesenchymal transition, proliferation, invasion, migration, angiogenesis, and metastasis), and the high diagnostic potential of exosomal microRNAs for detecting early BC.

Keywords: EVs; blood; breast cancer; exosomes; liquid biopsy; microRNA

DOI: https://doi.org/10.3390/molecules30193858

Int J Mol Sci. 2025 Sep 24. pii: 9323. [Epub ahead of print]26(19):

Exosomal miRNAs: Key Regulators of the Tumor Microenvironment and Cancer Stem Cells.

Shuangmin Wang, Sikan Jin, Jidong Zhang, Xianyao Wang.

Exosomes are lipid bilayer vesicles approximately 30-150 nm in diameter that serve as key mediators of intercellular communication. By transporting diverse bioactive molecules, including proteins and nucleic acids, they play a crucial role in tumor initiation and progression. Among their functional cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and intercellular signaling, significantly influencing tumor biology. This review provides a comprehensive overview of the multifaceted roles of exosomal miRNAs in remodeling the tumor microenvironment (TME) and regulating cancer stem cells (CSCs). Specifically, exosomal miRNAs modulate various immune cells (such as macrophages, T cells, and NK cells) as well as cancer-associated fibroblasts (CAFs), thereby promoting immune evasion, angiogenesis, epithelial-mesenchymal transition (EMT), and metastatic progression. At the same time, they enhance CSC stemness, self-renewal, and therapeutic resistance, ultimately driving tumor recurrence and dissemination. Furthermore, exosome-mediated miRNA signaling acts as a critical force in malignant progression. Finally, we discuss the clinical potential of exosomal miRNAs as diagnostic and prognostic biomarkers, therapeutic targets, and vehicles for targeted drug delivery, highlighting their translational value and future directions in cancer research.

Keywords: CSCs; cancer; exosomes; miRNA

DOI: https://doi.org/10.3390/ijms26199323

IUBMB Life. 2025 Oct;77(10): e70062

Gastric Cancer Cell-Derived Exosomes Induce Macrophage M2 Polarization by Delivering circSMARCC1 to Promote Gastric Cancer Progression.

Cao Zhang, Jingjing Ye, Qingsong Guan, Xiuyi Fang.

Exosomes, the cargo of circRNA, are crucial in cancer cell-tumor microenvironment communication. circSMARCC1 exerts a pro-tumor effect. However, this role has not been previously reported in gastric cancer (STAD). This study explores the role of STAD cell-derived exosomal circSMARCC1 in promoting macrophage M2 polarization. In this study, exosomes from the peripheral blood of STAD patients and AGS cells were extracted and identified. THP-1 cells were differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and polarized to the M2 phenotype by IL-4 and IL-13. circSMARCC1 expression was analyzed in STAD tissues, cell lines, and patient-derived exosomes. The biological function of circSMARCC1 in STAD cells was evaluated by CCK-8, EdU, and Transwell assays. The role of circSMARCC1 and U2 small nuclear RNA auxiliary factor 2 (U2AF2) in regulating macrophage M2 polarization was verified by bioinformatics methods, qRT-PCR, Western blot, ELISA, and a nude mouse tumor-bearing model. Our findings demonstrated that circSMARCC1 was upregulated in STAD and associated with macrophage immune infiltration. circSMARCC1 knockdown suppressed the malignant phenotypes of STAD cells and M2 macrophage polarization, whereas its overexpression led to the contrary result. Animal experiments further confirmed circSMARCC1 regulated tumor growth and macrophage M2 polarization. Importantly, exosomal circSMARCC1 in STAD patients was increased. Knockdown of circSMARCC1 in AGS cells reduced its level in secreted exosomes and inhibited M2 polarization, whereas overexpression produced the opposite effect. Mechanistically, circSMARCC1 upregulated U2AF2 expression through exosomes to promote macrophage M2 polarization. Collectively, STAD cell-derived exosomes induced macrophage M2 polarization to promote STAD progression through circSMARCC1.

Keywords: U2AF2; circSMARCC1; exosomes; gastric cancer; macrophages M2 polarization

DOI: https://doi.org/10.1002/iub.70062

Front Immunol. 2025 ;16 1677088

Exosomal biomarkers in leukemia: translational potential and regulatory challenges for precision medicine applications.

Mohammad Amin Ansarian, Mahsa Fatahichegeni, Yuqi Wang, Juan Ren, Tongxin Zhang, Xiaoning Wang.

Exosomes represent a paradigm shift in leukemia biomarker research, evolving from overlooked cellular waste products to sophisticated intercellular messengers with significant clinical implications for hematological malignancies. These membrane-bound vesicles carry disease-specific molecular cargo, including proteins, lipids, and nucleic acids that mirror leukemic cell pathology, making them accessible through minimally invasive liquid biopsies. Current evidence demonstrates characteristic molecular signatures across different leukemia subtypes, with exosomal microRNAs such as miR-150, miR-155, and the miR-29 family showing diagnostic and prognostic value, while protein markers including CD19, CD20, and IFITM3 correlate with disease status and therapeutic responses. Beyond diagnostic applications, exosomes orchestrate complex biological processes that reshape the bone marrow microenvironment, facilitate immune evasion, and promote treatment resistance through intercellular molecular exchange, presenting both challenges and therapeutic opportunities. Clinical translation has gained momentum through European regulatory frameworks, with exosomes classified as advanced therapy medicinal products under EMA guidelines. Early clinical trials demonstrate safety and feasibility, while diagnostic precedents like the ExoDx Prostate Test provide regulatory pathways for implementation. However, significant obstacles persist, including standardization of isolation methods, validation of biomarker panels, and integration with existing clinical decision algorithms. European collaborative initiatives through organizations like ISEV-ELBS and the HARMONY consortium address these challenges by establishing standardized protocols and conducting multi-center validation studies. The integration of artificial intelligence and machine learning approaches offers transformative potential for addressing clinical implementation challenges, with algorithms demonstrating superior discrimination capabilities and standardization solutions. While most exosomal biomarkers remain in early validation phases requiring comprehensive clinical development, the convergence of advancing analytical technologies, evolving regulatory frameworks, and collaborative research initiatives positions exosomes as promising tools for advancing precision medicine in leukemia. However, realistic timelines and sustained investment in methodological standardization remain essential for successful clinical translation.

Keywords: biomarkers; clinical translation; exosomes; leukemia; liquid biopsy; precision medicine; regulatory pathways

DOI: https://doi.org/10.3389/fimmu.2025.1677088

Transl Oncol. 2025 Oct 16. pii: S1936-5233(25)00295-5. [Epub ahead of print]62 102564

Tumor-derived exosomal miR-199b-5p promotes proliferation and epithelial-mesenchymal transition in non-small cell lung cancer by targeting CCNL1.

Bangzhu Liu, Yan Rui, Miao Li, Linian Huang.

OBJECTIVE: To explore the effect of exosome-mediated miR-199b-5p on lung cancer cells behavior, intrapulmonary metastasis, and its underlying mechanism.
METHODS: Exosomes from SK-LU-1 cells overexpressing has-miR-199b-5p (miR-199b-5p) were used to treat A549 or H299 cells. Cell motility was evaluated using wound scratch healing and transwell assays. Gene and protein expression were detected by quantitative real-time PCR (QRT-PCR) and Western blot. Target genes of miR-199b-5p were predicted through multiple-database analysis and validated.
RESULTS: Transmission electron microscopy (TEM) demonstrated isolated exosomes had a typical bilayer membrane (30-100 nm). miR-199b-5p was highly expressed in lung cancer cells and detectable in the serum of lung cancer patients, with the highest levels observed in SK-LU-1 cells and their derived exosomes. Exosomal miR-199b-5p significantly enhanced the motility of A549 and H1299 cells and upregulated the expression of epithelial-mesenchymal transition (EMT)-related proteins. Exosomes promoted lung metastasis of H1299 cells and inhibited the expression of Cyclin L1 (CCNL1). Either CCNL1 inhibition or miR-199b-5p overexpression significantly promoted H1299 cell proliferation and reduced apoptosis, while CCNL1 overexpression inhibited cell motility. Protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated involvement of the Wnt/β-catenin signaling pathway in the downstream mechanism. Mechanistically, miR-199b-5p inhibited cyclin-dependent kinase 11 (CDK11) and upregulated the expression of transcription factor 4 (TCF-4) and β-catenin.
CONCLUSIONS: Overexpression of miR-199b-5p promotes proliferation, migration, and EMT in lung cancer cells by targeting CCNL1, with its downstream regulatory effects mediated through the Wnt/β-catenin signaling.

Keywords: Cell cycle; Epithelial-mesenchymal transition; Exosomes; Wnt/β-catenin

DOI: https://doi.org/10.1016/j.tranon.2025.102564