Extracellular Vesicle RNA: A Key Player in the Tumor Microenvironment and Cancer Metastasis

Cancer progression is increasingly recognized as a dynamic process driven not only by malignant cells, but also by reciprocal interactions within the tumor microenvironment. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as key mediators of this intercellular communication by transporting bioactive cargo between neighboring and distant cells. Among these cargos, EV-associated RNAs - such as microRNAs, long non-coding RNAs, circular RNAs, messenger RNAs, and other small RNA species - can modulate stromal, immune, and endothelial cell behavior, thereby influencing angiogenesis, immune escape, invasion, and metastatic dissemination. At the same time, the remarkable stability of EV RNAs in blood and other biofluids has generated growing interest in their potential as minimally invasive biomarkers. Understanding the functional role of EV RNA is therefore essential for both mechanistic insight and clinical translation in cancer.This Research Topic aims to provide a dedicated platform for emerging studies on how EV-associated RNAs shape the tumor microenvironment and contribute to cancer metastasis. Although the field has advanced rapidly, important questions remain regarding the mechanisms governing RNA sorting into EVs, the heterogeneity of EV subpopulations, the specificity and efficiency of RNA transfer, and the biological impact of EV RNA in recipient cells. In parallel, technical challenges in EV isolation, characterization, and functional analysis continue to affect reproducibility and hinder cross-study comparison. Recent advances in RNA sequencing, single-vesicle and single-cell profiling, spatial omics, high-resolution imaging, organoid systems, and in vivo tracing now offer powerful opportunities to address these gaps. By bringing together basic, translational, and clinical research, this Research Topic seeks to highlight robust mechanistic insights, identify clinically relevant EV RNA signatures, and accelerate the development of EV RNA-based diagnostic and therapeutic approaches.We welcome submissions addressing the role of EV RNA in tumor progression, metastatic spread, and therapeutic response. Topics of interest include, but are not limited to: • EV biogenesis and RNA cargo selection; • mechanisms of EV secretion, uptake, and cargo release; • EV RNA-mediated communication between tumor, stromal, immune, endothelial, and niche cells; • functional roles of miRNAs, lncRNAs, circRNAs, mRNAs, tRNA-derived fragments, and other RNA species;• EV RNA in angiogenesis, immune modulation, metabolic reprogramming, dormancy, therapy resistance, and organ-specific metastasis; • liquid biopsy applications and biomarker discovery; and emerging technologies, computational approaches, and engineered EV platforms for therapy. We welcome Original Research, Review, Mini Review, Methods, and Perspective articles. Studies using patient samples, preclinical models, and advanced in vitro systems are particularly encouraged, and authors are advised to follow current MISEV recommendations where appropriate. Topic editors: Sze Keong Tey, Yi Xu, Yue Yao, Hassan Dastsooz Source: https://www.frontiersin.org/research-topics/80319/extracellular-vesicle-rna-a-key-player-in-the-tumor-microenvironment-and-cancer-metastasis