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

Published on Jul 1, 2021in Digestive Diseases and Sciences2.751
· DOI :10.1007/S10620-020-06518-6
Xiaoling Ding3
Estimated H-index: 3
(Nantong University),
Jie Zhang7
Estimated H-index: 7
(Nantong University)
+ 2 AuthorsXiaorong Zhou4
Estimated H-index: 4
(Nantong University)
Sources
Abstract
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. 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. 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. 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. 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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