MicroRNA-17-5p regulates EMT by targeting vimentin in colorectal cancer
Background Epithelial–mesenchymal transition (EMT) is the most common cause of death in colorectal cancer (CRC). In this study, we investigated the functional roles of miRNA-17-5p in EMT of CRC cells. Methods In order to determine if miRNA-17-5p regulated EMT, the precursors and inhibitors of miR-17...
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Veröffentlicht in: | British journal of cancer 2020-09, Vol.123 (7), p.1123-1130 |
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Sprache: | eng |
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Zusammenfassung: | Background
Epithelial–mesenchymal transition (EMT) is the most common cause of death in colorectal cancer (CRC). In this study, we investigated the functional roles of miRNA-17-5p in EMT of CRC cells.
Methods
In order to determine if miRNA-17-5p regulated EMT, the precursors and inhibitors of miR-17-5p were transduced into four CRC cells. To evaluate the regulatory mechanism, we performed argonaute 2 (Ago2) immunoprecipitation (IP) and luciferase assay. In addition, we used an intra-splenic injection mouse model of BALB/c nude mice to investigate the metastatic potential of miRNA-17-5p in vivo.
Results
The miRNA-17-5p expression was lower in primary CRC tissues with metastasis than in primary CRC tissues without metastasis in our RNA sequencing data of patient tissue. Real-time quantitative PCR revealed that miRNA-17-5p was inversely correlated with that of vimentin in five CRC cell lines. Over-expression of miRNA-17-5p decreased vimentin expression and inhibited cell migration and invasion in both LoVo and HT29 cells. However, inhibition of miRNA-17-5p showed the opposite effect. Ago2 IP and luciferase assay revealed that miRNA-17-5p directly bound to the 3′UTR of
VIM
mRNA. Furthermore, miRNA-17-5p inhibited the metastasis of CRC into liver in vivo.
Conclusions
Our results demonstrated that miRNA-17-5p regulates vimentin expression, thereby regulating metastasis of CRC. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/s41416-020-0940-5 |