Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases
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Updated: Dec 23, 2025

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Published on: October 6, 2023
1Department of Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Abstract:
Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.
Insights
Cells package microRNAs (miRNAs) into extracellular vesicles (EVs) for intercellular communication. Dysregulation of this EV-miRNA sorting is implicated in various diseases, highlighting its pathogenic role.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Extracellular vesicles (EVs) are key mediators of intercellular communication.
- EVs transport various biomolecules, including microRNAs (miRNAs), influencing recipient cell function.
- Recent research focuses on the selective sorting of miRNAs into EVs.
Purpose of the Study:
- To review the mechanisms of selective miRNA sorting into EVs.
- To outline disease states associated with dysregulated EV-miRNA content.
Main Methods:
- Literature review of studies on EV biogenesis and miRNA sorting.
- Analysis of RNA-binding proteins and EV-associated proteins involved in miRNA selection.
- Examination of disease-associated changes in EV-miRNA profiles.
Main Results:
- Specific proteins like hnRNPA2B1, Argonaute-2, Caveolin-1, and Neural Sphingomyelinase 2 are involved in selective miRNA sorting into EVs.
- Dysregulated EV-miRNA content is observed in chronic lung disease, immune disorders, neuroinflammation, diabetes, cancer, and heart disease.
- Selective sorting mechanisms are crucial for EV-miRNA cargo loading.
Conclusions:
- Cells actively and selectively package miRNAs into EVs.
- Aberrant EV-miRNA sorting contributes to the pathogenesis of multiple diseases.
- Understanding these mechanisms offers insights into disease development and potential therapeutic targets.
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