摘要：SummaryCirculating extracellular vesicles (EVs) contain molecular footprints—lipids, proteins, RNA, and DNA—from their cell of origin. Consequently, EV-associated RNA and proteins have gained widespread interest as liquid-biopsy biomarkers. Yet, an integrative proteo-transcriptomic landscape of EVs and comparison with their cell of origin remains obscure. Here, we report that EVs enrich distinct proteo-transcriptome that does not linearly correlate with their cell of origin. We show that EVs enrich endosomal and extracellular proteins, small RNA (∼13–200 nucleotides) associated with cell differentiation, development, and Wnt signaling. EVs cargo specific RNAs (RNY3, vtRNA, and MIRLET-7) and their complementary proteins (YBX1, IGF2BP2, and SRSF1/2). To ensure an unbiased and independent analyses, we studied 12 cancer cell lines, matching EVs (inhouse and exRNA database), and serum EVs of patients with prostate cancer. Together, we show that EV-RNA-protein complexes may constitute a functional interaction network to protect and regulate molecular access until a function is achieved.Graphical abstractDisplay OmittedHighlights•Extracellular vesicles (EVs) enrich unique RNA & proteins compared to cell of origin•EVs enrich small coding/noncoding RNAs (13–200 nt) associated with cell development•Blood EVs of patients with prostate cancer reveal immune regulation function•EVs RNA-proteins are inter-related and show functional interaction networkCancer systems biology; Microenvironment; Transcriptomics
