Circular RNA landscape in extracellular vesicles from human biofluids - Details

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Abstract：

Background:　Circular　RNAs　(circRNAs)　have　emerged　as　a　prominent　class　of　covalently　closed　single-stranded　RNA　molecules　that　exhibit　tissue-specific　expression　and　potential　as　biomarkers　in　extracellular　vesicles　(EVs)　derived　from　liquid　biopsies.　Still,　their　characteristics　and　applications　in　EVs　remain　to　be　unveiled.　Methods:　We　performed　a　comprehensive　analysis　of　EV-derived　circRNAs　(EV-circRNAs)　using　transcriptomics　data　obtained　from　1082　human　body　fluids,　including　plasma,　urine,　cerebrospinal　fluid　(CSF),　and　bile.　Our　validation　strategy　utilized　RT-qPCR　and　RNA　immunoprecipitation　assays,　complemented　by　computational　techniques　for　analyzing　EV-circRNA　features　and　RNA-binding　protein　interactions.　Results:　We　identified　136,327　EV-circRNAs　from　various　human　body　fluids.　Significantly,　a　considerable　amount　of　circRNAs　with　a　high　back-splicing　ratio　are　highly　enriched　in　EVs　compared　to　linear　RNAs.　Additionally,　we　discovered　brain-specific　circRNAs　enriched　in　plasma　EVs　and　cancer-associated　EV-circRNAs　linked　to　clinical　outcomes.　Moreover,　we　demonstrated　that　EV-circRNAs　have　the　potential　to　serve　as　biomarkers　for　evaluating　immunotherapy　efficacy　in　non-small　cell　lung　cancer　(NSCLC).　Importantly,　we　identified　the　involvement　of　RBPs,　particularly　YBX1,　in　the　sorting　mechanism　of　circRNAs　into　EVs.　Conclusions:　This　study　unveils　the　extensive　repertoire　of　EV-circRNAs　across　human　biofluids,　offering　insights　into　their　potential　as　disease　biomarkers　and　their　mechanistic　roles　within　EVs.　The　identification　of　specific　circRNAs　and　the　elucidation　of　RBP-mediated　sorting　mechanisms　open　new　avenues　for　the　clinical　application　of　EV-circRNAs　in　disease　diagnostics　and　therapeutics.　©　The　Author(s)　2024.

Keyword：

Biomarker Cancer Circular RNAs Extracellular vesicles RNA-binding proteins

Community：

[ 1 ] [Zhao J.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 2 ] [Zhao J.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 3 ] [Li Q.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 4 ] [Li Q.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 5 ] [Hu J.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 6 ] [Hu J.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 7 ] [Yu H.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 8 ] [Yu H.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 9 ] [Shen Y.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 10 ] [Shen Y.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 11 ] [Lai H.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 12 ] [Lai H.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 13 ] [Li Q.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 14 ] [Li Q.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 15 ] [Zhang H.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 16 ] [Zhang H.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 17 ] [Li Y.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 18 ] [Li Y.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
[ 19 ] [Fang Z.]Department of Oncology and Vascular Interventional Therapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital (Fujian Branch of Fudan University Shanghai Cancer Center), Fuzhou, 350014, China
[ 20 ] [Fang Z.]Department of Interventional Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
[ 21 ] [Huang S.]Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
[ 22 ] [Huang S.]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

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