Circular RNA landscape in extracellular vesicles from human biofluids

Jingjing Zhao ^1,2, Qiaojuan Li ^1,2, Jia Hu ^1,2

⁰Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.

Genome Medicine +

|

November 1, 2024

View abstract on PubMed

Summary

Extracellular vesicle (EV)-derived circular RNAs (circRNAs) from human biofluids show potential as disease biomarkers. This study identified numerous EV-circRNAs and elucidated RNA-binding protein mechanisms for their sorting into EVs.

Area Of Science

Biochemistry
Molecular Biology
Genomics

Background

Circular RNAs (circRNAs) are covalently closed, single-stranded RNA molecules with tissue-specific expression.
Extracellular vesicles (EVs) derived from liquid biopsies are promising sources for biomarker discovery.
The characteristics and roles of circRNAs within EVs remain largely unexplored.

Purpose Of The Study

To comprehensively analyze extracellular vesicle-derived circRNAs (EV-circRNAs) across diverse human biofluids.
To investigate the potential of EV-circRNAs as biomarkers for disease diagnosis and treatment efficacy.
To elucidate the mechanisms governing the sorting of circRNAs into EVs.

Main Methods

Transcriptomic analysis of 1082 human biofluid samples (plasma, urine, CSF, bile).
Validation using RT-qPCR and RNA immunoprecipitation (RIP) assays.
Computational analysis of EV-circRNA features and RNA-binding protein (RBP) interactions.

Main Results

Identification of 136,327 unique EV-circRNAs across human biofluids.
High enrichment of circRNAs with high back-splicing ratios in EVs compared to linear RNAs.
Discovery of brain-specific and cancer-associated EV-circRNAs, with potential for non-small cell lung cancer (NSCLC) immunotherapy efficacy assessment.
Identification of YBX1 as a key RBP involved in EV-circRNA sorting.

Conclusions

This study reveals an extensive repertoire of EV-circRNAs with significant potential as disease biomarkers.
Elucidation of RBP-mediated sorting mechanisms provides insights into EV-circRNA biogenesis.
These findings open new avenues for the clinical application of EV-circRNAs in diagnostics and therapeutics.

Keywords:

Biomarker Cancer Circular RNAs Extracellular vesicles RNA-binding proteins

Related Concept Videos

Overview of Exosomes

Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...