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

Digestive Diseases and Sciences volume 66, pages 2272–2282 (2021)Cite this article

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China [Grant Number 81771681]; Jiangsu Six Elite Units Foundation [Grant Number WSW-058].

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Affiliations

  1. Department of Gastroenterology, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China

    Xiaoling Ding

  2. Department of Immunology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, 226019, Jiangsu, China

    Jie Zhang & Xiaorong Zhou

  3. School of Medicine, Nantong University, Nantong, 226019, Jiangsu, China

    Ziqin Feng & Qianru Tang

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  1. Xiaoling Ding
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Correspondence to Xiaorong Zhou.

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Ding, X., Zhang, J., Feng, Z. et al. MiR-137-3p Inhibits Colorectal Cancer Cell Migration by Regulating a KDM1A-Dependent Epithelial–Mesenchymal Transition. Dig Dis Sci 66, 2272–2282 (2021). https://doi.org/10.1007/s10620-020-06518-6

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  • DOI: https://doi.org/10.1007/s10620-020-06518-6

Keywords

  • Colorectal neoplasms
  • MicroRNAs
  • Epithelial–mesenchymal transition
  • Histone lysine demethylases
  • Neoplasm metastasis