Genetics and Genomics

MicroRNA-17-5p regulates EMT by targeting vimentin in colorectal cancer

A Correction to this article was published on 20 August 2020

This article has been updated

Abstract

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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Fig. 1: miR-17-5p is inversely correlated with the expression of vimentin in colon cancer cells.
Fig. 2: Regulation of vimentin expression by miR-17-5p in CRC cell lines.
Fig. 3: Direct targeting of miR-17-5p to the 3′UTR of VIM mRNA.
Fig. 4: Control of cell migration and invasion by miR-17-5p.
Fig. 5: Inhibition of liver metastasis by miR-17-5p.

Change history

  • 20 August 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

The biospecimens for this study were provided by the Samsung Medical Center BioBank (20130014 and 20140001).

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Authors

Contributions

T.W.K., Y.S.L., and Y.B.C. conceived the study design. T.W.K., Y.S.L., N.H.Y., C.H.S., and H.K.H. conducted the experiments. T.W.K. wrote the initial manuscript drafts. Y.S.L., H.H.K., and Y.B.C. performed critical editing. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Hyeon Ho Kim or Yong Beom Cho.

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Ethics approval and consent to participate

Ethics approval for animal use was obtained from the Samsung Medical Center on Laboratory Animals Committee (approval number: 20180129002). We carried out animal experiments in accordance with the ARRIVE reporting guideline and Samsung Medical Center on Laboratory Animals Committee’s guideline.

Data availability

The data supporting the finding of this study are available within the article and are available from the corresponding authors upon request.

Competing interests

The authors declare no competing interests.

Funding information

This paper was supported by the Sungkyun Research Fund, Sungkyunkwan University, 2018.

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Kim, T.W., Lee, Y.S., Yun, N.H. et al. MicroRNA-17-5p regulates EMT by targeting vimentin in colorectal cancer. Br J Cancer 123, 1123–1130 (2020). https://doi.org/10.1038/s41416-020-0940-5

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