MiR-204-5p/Six1 feedback loop promotes epithelial–mesenchymal transition in breast cancer
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Epithelial–mesenchymal transition (EMT) is a vital process in epithelial cancer invasion and metastasis. The induction of EMT by Six1 has been described as a common mode of cancer progression, which could promote breast cancer migration and invasion. In the study, we found that miR-204-5p could suppress the migration and invasion of breast cancer cell lines. Since overexpression of Six1 promote EMT, we identified a mechanism by which miR-204-5p inhibited the EMT by downregulating the Six1, which was mediated by a conserved miR-204-5p seed-matching sequence in the 3′-UTR of Six1 mRNA. We also identified that upregulation of Six1 could downregulate miR-204-5p expression, affecting the migration and invasion of breast cancer cell lines. In conclusion, the frequent upregulation of Six1 and/or downregulation of miR-204-5p in breast cancer may shift the equilibrium of these reciprocal regulations and lock breast cancer cells in the mesenchymal state.
KeywordsmiR-204-5p Six1 EMT Breast cancer
JZ and MW designed all the experiments. JZ, MW, and RS performed clinical data acquisition, statistical analysis, and drafted the manuscript. CXC and XRL performed experiment studies. YBS and WLZ performed critical revision. WLM designed and directed the study. All authors read and approved the final manuscript.
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