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EMT-cancer cells-derived exosomal miR-27b-3p promotes circulating tumour cells-mediatedmetastasis by modulating vascular permeability in colorectal cancer.
- Source :
-
Clinical & Translational Medicine . Dec2021, Vol. 11 Issue 12, p1-22. 22p. - Publication Year :
- 2021
-
Abstract
- Background: Metastasis is the main cause of death in colorectal cancer (CRC). Circulating tumour cells (CTCs) are regarded as the precursor cells of metastasis. The CTCs, which underwent epithelial-mesenchymal transition (EMT), are associated with metastasis and responsible for poor prognosis. EMT cancer cells modulate endothelial permeability in the invasive front and facilitate cancer cell intravasation, resulting in CTCs-mediated distant metastasis. Exosomes derived from cancer cells are key mediators of cancer-host intercommunication. However, the mechanism by which EMT-tumour cells-derived exosomes modulate vascular permeability and promote CTCs generation has remained unclear. Methods: Exosomes isolation and purification were conducted by ultracentrifugation. Exosomal miRNA was identified by sequencing followed by quantitative PCR. In vitro co-culture assay experiments were conducted to evaluate the effect of exosomal miR-27b-3p on the permeability of blood vessel endothelium. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were performed to investigate the underlying mechanism by which miR-27b-3p is packaged into exosomes. A mouse model was established to determine the role of exosomal miR-27b-3p in blood vessel permeability modulation in vivo. Results: We found that EMT-CRC cells attenuate the blood vessel barrier by transferring miR-27b-3p to human umbilical vein endothelial cells (HUVECs) in exosomes. Mechanically, miR-27b-3p atteuated the expression of vascular endothelial cadherin (VE-Cad) and p120 at the post-transcriptional level by binding to 3'-untranslated region of VE-Cad and p120 directly. The packaging of miR-27b-3p into exosomes was induced by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which activated by STAT3. Clinically, miR-27b-3p up-regulated in CRC tissues. Plasma exosomal miR-27b-3p was positively correlated with malignant progression and CTC count in CRC patients. Our study reveals a novel mechanism by which EMT-CRC cells promote metastasis, increasing blood vessel permeability and facilitating the generation of CTCs. Conclusion: Exosomal miR-27b-3p secreted by EMT-CRC cells increases blood vessel permeability and facilitates the generation of CTCs. ExosomalmiR-27b-3p may become a promising biomarker for CRC metastasis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MICRORNA
*VASCULAR endothelium
*COLORECTAL cancer
*EXOSOMES
*PERMEABILITY
Subjects
Details
- Language :
- English
- ISSN :
- 20011326
- Volume :
- 11
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Clinical & Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 154646392
- Full Text :
- https://doi.org/10.1002/ctm2.595