Extracellular vesicle-mediated intercellular epigenetic communication in cancer pathogenesis

Abstract

Extracellular vesicles (EVs) are lipid bilayer nanoparticles secreted by almost all cell types, serving as vital mediators of intercellular communication by transporting bioactive cargos, including proteins, lipids, and nucleic acids. This review summarizes the emerging role of EVs as pivotal carriers in cancer epigenetic regulation, focusing on their functions in cancer pathogenesis through the delivery of non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as well as the modulation of DNA methylation and histone modifications. Drawing on evidence from various malignancies (including osteosarcoma, breast cancer, gastric cancer, hepatocellular carcinoma, cervical cancer, lung cancer, pancreatic cancer, colorectal cancer, bladder cancer, and esophageal squamous cell carcinoma), we systematically elucidate how tumor- or matrix-derived EVs promote tumor progression by delivering specific epigenetic regulators (e.g., NORAD, miR-3190, and circ_0064516). These EV-encapsulated molecules can inhibit tumor suppressors, activate oncogenic pathways (such as PI3K/AKT and Wnt/β-catenin), and promote epithelial-mesenchymal transition, angiogenesis, immune evasion, and metastasis. Furthermore, EVs reshape the epigenetic landscape of the tumor microenvironment by inducing genomic DNA hypomethylation (e.g., LINE-1) and altering histone modifications. Finally, we discuss the potential of EV-associated epigenetic molecules as diagnostic biomarkers and therapeutic targets, underscoring the clinical significance of EVs as key information carriers in oncology.

Keywords

Extracellular vesicles / Cancer epigenetics / Non-coding RNAs / Tumor microenvironment / Biomarkers

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Funding

National Natural Science Foundation of China(32270832)

Noncommunicable Chronic Diseases-National Science and Technology Major Project(2025ZD0549800)

Guangdong Basic and Applied Basic Research Foundation(2023B1515020039)

Shenzhen Science and Technology Program(RCYX20221008092904016)

Shenzhen University 2035 Program for Excellent Research(2022C012)

the Program for Youzuzhikeyan of Shenzhen University(the Program for Youzuzhikeyan of Shenzhen University)

RIGHTS & PERMISSIONS

Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare