Journal
DIGESTIVE DISEASES AND SCIENCES
Volume 66, Issue 7, Pages 2272-2282Publisher
SPRINGER
DOI: 10.1007/s10620-020-06518-6
Keywords
Colorectal neoplasms; MicroRNAs; Epithelial-mesenchymal transition; Histone lysine demethylases; Neoplasm metastasis
Categories
Funding
- National Natural Science Foundation of China [81771681]
- Jiangsu Six Elite Units Foundation [WSW-058]
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In colorectal cancer, the downregulation of miR-137-3p and upregulation of KDM1A are associated with disease progression. Inhibiting miR-137-3p leads to increased KDM1A expression and promotes CRC cell invasiveness. Targeting KDM1A inhibits CRC cell migration and invasion by regulating the EMT process.
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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