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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 7/2021

01-07-2021 | Metastasis | Original Article

MiR-137-3p Inhibits Colorectal Cancer Cell Migration by Regulating a KDM1A-Dependent Epithelial–Mesenchymal Transition

Authors: Xiaoling Ding, Jie Zhang, Ziqin Feng, Qianru Tang, Xiaorong Zhou

Published in: Digestive Diseases and Sciences | Issue 7/2021

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Abstract

Background

In colorectal cancer (CRC), miR-137-3p downregulation is associated with disease progression, but the mechanism is not fully understood. KDM1A, also known as LSD1, is upregulated in various cancer and promotes tumor metastasis. Interestingly, miR-137-3p is downregulated by hypoxia, which plays critical roles in tumor metastasis, and KDM1A is a miR-137-3p target gene in brain tumors.

Aims

To study if CRC metastasis is regulated by a hypoxia/miR-137-3p/KDM1A axis and if the epithelial–mesenchymal transition (EMT) process is involved.

Methods

We measured the levels of miR-137-3p, KDM1A, and some EMT markers in CRC biopsy tissues and cell lines. We also investigated the regulation of KDM1A by miR-137-3p and the effects of KDM1A inhibition on the EMT process and cell migration.

Results

We verified the low miR-137-3p and high KDM1A levels in CRC tumors. Inhibiting miR-137-3p upregulated KDM1A expression and promoted the invasiveness of CRC cells. KDM1A knockdown, or treatment with tranylcypromine, a specific KDM1A inhibitor, reduced the migration and invasion of CRC cells by inhibiting the EMT process. CRC cells cultured under hypoxic conditions expressed less miR-137-3p but more KDM1A than cells cultured under normal conditions, implying the involvement of miR-137-3p and KDM1A in hypoxia-induced tumor metastasis.

Conclusions

We conclude that MiR-137-3p inhibits CRC cell migration by regulating a KDM1A-dependent EMT process. Our study suggests that restoring the expression of miR-137-3p or targeting KDM1A might be potential therapeutic strategies for CRC.
Appendix
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Metadata
Title
MiR-137-3p Inhibits Colorectal Cancer Cell Migration by Regulating a KDM1A-Dependent Epithelial–Mesenchymal Transition
Authors
Xiaoling Ding
Jie Zhang
Ziqin Feng
Qianru Tang
Xiaorong Zhou
Publication date
01-07-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06518-6

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