miR-1-3p targets GLIS1 to reverse epithelial-mesenchymal transition (EMT) and inhibit invasion and metastasis in breast cancer

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Abstract

This study reveals for the first time a new mechanism by which miR-1-3p targets GLIS1 to reverse EMT. This reversal inhibits breast cancer invasion and metastasis.Through the integration of TCGA database analysis, clinical sample validation (n = 60), and multidimensional functional experiments, we found that: the expression of miR-1-3p is significantly lower in breast cancer tissues compared to adjacent tissues, and it is significantly negatively correlated with tumor stage; Overexpression of miR-1-3p can inhibit the proliferation of MDA-MB-231 cells and reduce their invasion and migration abilities; Bioinformatics predictions combined with dual-luciferase reporter gene experiments confirmed GLIS1 is a direct target gene of miR-1-3p; Mechanistic studies indicate that miR-1-3p reverses the EMT process by inhibiting the GLIS1/β-catenin axis (downregulation of β-catenin protein), leading to upregulation of E-cadherin and downregulation of N-cadherin/Vimentin. This study elucidates the critical role of the miR-1-3p-GLIS1-β-catenin regulatory axis in breast cancer metastasis, providing a new strategy for targeted EMT therapy.

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