Published in:
01-06-2021 | Metastasis | Original Article
Mesenchymal Stem Cell-Derived Exosomal microRNA-3940-5p Inhibits Colorectal Cancer Metastasis by Targeting Integrin α6
Published in: Digestive Diseases and Sciences | Issue 6/2021
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Background
Exosomes are potential tools for disease control by regulating intercellular communication through carrying proteins and RNAs between cells or remote organs. Exosome activities have aroused wide concerns in cancer biology and malignancy control.
Aims
This study was performed to explore the roles of mesenchymal stem cell (MSC)-derived exosomes in colorectal cancer (CRC) progression.
Methods
MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed, and aberrantly expressed miRNAs in CRC tissues were obtained from the data available on the GEO database. Altered expression of miR-3940-5p was introduced to identify its role in CRC invasion and metastasis in both cell and animal models. The binding relationship between miR-3940-5p and Integrin alpha6 (ITGA6) was predicted on TargetScan and validated through a luciferase assay. The effects of ITGA6 on CRC were figured out.
Results
MSC-derived exosomes carried miR-3940-5p into CRC cells. Up-regulation of miR-3940-5p inhibited epithelial–mesenchymal transition (EMT) and invasion of CRC cells, and suppressed the tumor metastasis and growth in vivo. miR-3940-5p was found to directly bind to ITGA6. Overexpression of ITGA6 promoted CRC cell invasion and EMT and tumor progression through upregulating the transforming growth factor-beta1 (TGF-β1) signaling. A TGF-β1-specific antagonist, Disitertide, blocked the functions of ITGA6 both in vivo and in vitro.
Conclusion
MSC-exosomal miR-3940-5p inhibits invasion and EMT of CRC cells as well as growth and metastasis of tumors through targeting ITGA6 and the following TGF-β1 inactivation. This study may provide novel insights into exosome-based treatment for CRC.