Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun;66(6):1916-1927.
doi: 10.1007/s10620-020-06458-1. Epub 2020 Jul 15.

Mesenchymal Stem Cell-Derived Exosomal microRNA-3940-5p Inhibits Colorectal Cancer Metastasis by Targeting Integrin α6

Tao Li #  1 , Yingchun Wan #  2 , Ziyuan Su  3 , Jiayu Li  4 , Minna Han  5 , Changyu Zhou  6
Affiliations

Mesenchymal Stem Cell-Derived Exosomal microRNA-3940-5p Inhibits Colorectal Cancer Metastasis by Targeting Integrin α6

Tao Li et al. Dig Dis Sci. 2021 Jun.

Abstract

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.

Keywords: Colorectal cancer; Exosomes; Integrin alpha6; Mesenchymal stem cells; Transforming growth factor beta1; miR-3940-5p.

PubMed Disclaimer

References

    1. Ding D, Han S, Zhang H, He Y, Li Y. Predictive biomarkers of colorectal cancer. Comput Biol Chem. 2019;83:107106. - DOI
    1. Sun M, Liu J, Hu H, et al. A novel panel of stool-based DNA biomarkers for early screening of colorectal neoplasms in a Chinese population. J Cancer Res Clin Oncol. 2019;145:2423–2432. - DOI
    1. Zhang W, Sun Z, Su L, et al. miRNA-185 serves as a prognostic factor and suppresses migration and invasion through Wnt1 in colon cancer. Eur J Pharmacol. 2018;825:75–84. - DOI
    1. Hong Y, Rao Y. Current status of nanoscale drug delivery systems for colorectal cancer liver metastasis. Biomed Pharmacother. 2019;114:108764. - DOI
    1. Paauwe M, Schoonderwoerd MJA, Helderman R, et al. Endoglin expression on cancer-associated fibroblasts regulates invasion and stimulates colorectal cancer metastasis. Clin Cancer Res. 2018;24:6331–6344. - DOI

Publication types

LinkOut - more resources