In:
Journal of Biomedical Science, Springer Science and Business Media LLC, Vol. 27, No. 1 ( 2020-12)
Kurzfassung:
Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in many cancers. However, the role of MiRNA in FN assembly-related ESCC mobility remains unexplored. Methods We divided ESCC CE81T cells into high-FN assembly (CE81 FN+ ) and low-FN assembly (CE81 FN− ) groups by flow cytometry. MiRNA microarray analysis identified miR-146a expression as the most down-regulated miRNA in comparison of CE81 FN+ and CE81 FN− cells. Results Cell proliferation and migration were decreased when CE81 FN+ cells overexpressed transgenic miR-146a compared to the parental cells, indicating an inverse correlation between low miR-146a expression and high proliferation as well as motility of FN assembly ESCC cells. Furthermore, vimentin is the target gene of miR-146a involved in ESCC tumorigenesis. MiR-146a suppressed cell proliferation, migration and invasion of CE81 FN+ cells through the inhibition of vimentin expression, as confirmed by real-time PCR, Western blotting and Transwell™ assay. Analysis of one hundred and thirty-six paired ESCC patient specimens revealed that low miR-146a and high vimentin levels were frequently detected in tumor, and that the former was associated with late tumor stages (III and IV). Notably, either low miR-146a expression or high vimentin level was significantly associated with poor overall survival rate among ESCC patients. Conclusions This is the first report to link FN assembly in the cell membrane with miR-146a , vimentin and ESCC tumorigenesis both in vitro and in ESCC patients.
Materialart:
Online-Ressource
ISSN:
1423-0127
DOI:
10.1186/s12929-020-00693-4
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2020
ZDB Id:
1482918-6
