Related Experiment Video
Updated: May 20, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
MicroRNAs are exported from malignant cells in customized particles
Jaime Palma1, Sree C Yaddanapudi, Lucy Pigati
1Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
Abstract:
MicroRNAs (miRNAs) are released from cells in association with proteins or microvesicles. We previously reported that malignant transformation changes the assortment of released miRNAs by affecting whether a particular miRNA species is released or retained by the cell. How this selectivity occurs is unclear. Here we report that selectively exported miRNAs, whose release is increased in malignant cells, are packaged in structures that are different from those that carry neutrally released miRNAs (n-miRNAs), whose release is not affected by malignancy. By separating breast cancer cell microvesicles, we find that selectively released miRNAs associate with exosomes and nucleosomes. However, n-miRNAs of breast cancer cells associate with unconventional exosomes, which are larger than conventional exosomes and enriched in CD44, a protein relevant to breast cancer metastasis. Based on their large size, we call these vesicles L-exosomes. Contrary to the distribution of miRNAs among different microvesicles of breast cancer cells, normal cells release all measured miRNAs in a single type of vesicle. Our results suggest that malignant transformation alters the pathways through which specific miRNAs are exported from cells. These changes in the particles and their miRNA cargo could be used to detect the presence of malignant cells in the body.
Insights
Malignant cells release specific microRNAs (miRNAs) in larger vesicles called L-exosomes, unlike normal cells. This altered miRNA packaging could help detect cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- MicroRNAs (miRNAs) are released from cells via proteins or microvesicles.
- Malignant transformation alters the composition of released miRNAs, but the mechanism of selectivity is unknown.
- Previous work showed that malignancy affects miRNA release versus retention within cells.
Purpose of the Study:
- To investigate the mechanisms by which malignant cells selectively export specific microRNAs (miRNAs).
- To characterize the structures packaging selectively released miRNAs compared to neutrally released miRNAs (n-miRNAs).
- To explore the potential of these miRNA-packaging alterations for cancer detection.
Main Methods:
- Separation and analysis of microvesicles released from breast cancer cells.
- Characterization of miRNA association with different types of microvesicles, including exosomes and nucleosomes.
- Comparison of microvesicle composition and miRNA distribution between malignant and normal cells.
Main Results:
- Selectively exported miRNAs in malignant cells are packaged in distinct structures, including exosomes and nucleosomes.
- Neutrally released miRNAs (n-miRNAs) in breast cancer cells associate with larger, unconventional exosomes (L-exosomes) enriched in CD44.
- Normal cells release all measured miRNAs within a single type of vesicle, unlike the heterogeneous release in cancer cells.
Conclusions:
- Malignant transformation significantly alters cellular pathways for specific miRNA export.
- Distinct microvesicle populations (L-exosomes) carry specific miRNAs in cancer cells.
- These miRNA-associated microvesicles represent potential biomarkers for detecting malignant cells.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs