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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-...

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Detalles Bibliográficos
Autores principales: Kim, Tae Won, Lee, Yeo Song, Yun, Nak Hyeon, Shin, Chang Hoon, Hong, Hye Kyung, Kim, Hyeon Ho, Cho, Yong Beom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524803/
https://www.ncbi.nlm.nih.gov/pubmed/32546833
http://dx.doi.org/10.1038/s41416-020-0940-5
Descripción
Sumario: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.