MiR-142-3p targets the CXCL12/WNT/β-catenin pathway to regulate the stemness of breast cancer cells

TL;DR

This study shows that miR-142-3p reduces breast cancer cell growth and resistance by targeting the CXCL12/WNT/β-catenin pathway.

Contribution

The novel finding is that miR-142-3p regulates breast cancer progression via the CXCL12/WNT/β-catenin pathway and affects paclitaxel resistance.

Findings

miR-142-3p inhibits proliferation, migration, EMT, and stemness in MCF 7 breast cancer cells.

miR-142-3p targets CXCL12 and modulates the WNT/β-catenin signaling pathway.

miR-142-3p helps overcome paclitaxel resistance by reducing SOX2 protein levels.

Abstract

Breast cancer is the most common type of cancer among women. It is well-established that microRNAs (miRNAs) play a critical role in cancer development by either degrading messenger RNA (mRNA) or inhibiting its translation, thereby suppressing the expression of specific genes. In this study, we found that the expression level of miR-142-3p was significantly lower in breast cancer cells and tissues than in normal breast epithelial cells and adjacent tissues. We demonstrated that miR-142-3p could inhibit the proliferation, migration, epithelial-mesenchymal transition (EMT), and stemness of MCF 7 breast cancer cells, while also promoting apoptosis. Further investigation revealed that miR-142-3p directly targets CXCL12 and regulates its expression. Silencing CXCL12 (using CXCL12 siRNA) suppressed the migration, EMT, and stemness of MCF 7 cells, and these effects were reversed by inhibition of miR-142-3p. Additionally, we observed alterations in β-catenin protein levels, suggesting that miR-142-3p may modulate the WNT/β-catenin signaling pathway through targeting CXCL12 in MCF 7 cells. Subsequent experiments indicated that miR-142-3p also plays a crucial role in overcoming paclitaxel resistance in MCF 7/PTX cells. SOX2 protein levels, which are associated with paclitaxel resistance, proliferation, migration, and EMT, were higher in MCF 7/PTX cells compared to MCF 7 cells. Overall, our findings suggest that miR-142-3p influences breast cancer progression by targeting the CXCL12/WNT/β-catenin pathway, thereby affecting cell migration, EMT, stemness, and paclitaxel resistance.

The online version contains supplementary material available at 10.1038/s41598-025-34163-4.

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