RNF125 inhibits EMT and glycolysis in breast cancer by suppressing HDAC1-mediated histone deacetylation of PGM5.

BACKGROUND

Epithelial-mesenchymal transition (EMT) and glycolysis contribute to breast cancer (BC). However, the molecular mechanisms underlying these processes require further investigation.

METHODS

Gene abundance was determined using RT-qPCR, Western blotting, and IHC. Cell viability and migration were evaluated using CCK-8 and scratch tests. Co-IP was performed to confirm the RNF125-HDAC1 interaction. Glycolysis-related indicators were detected using commercial kits, the Seahorse XF assay, and Western blotting. The enrichment of H3K27ac in the PGM5 promoter was determined using ChIP.

RESULTS

In BC samples, RNF125 and PGM5 levels were downregulated, whereas HDAC1 expression was upregulated. Upregulation of RNF125 inhibited EMT and glycolysis in BC cells, suppressed tumor growth in subcutaneous tumor-bearing mouse models, and reduced lung metastasis in mice; these effects were counteracted by HDAC1 overexpression. Similarly, PGM5 overexpression suppressed EMT and glycolysis in BC cells; however, this suppression was blocked by HDAC1 overexpression or RNF125 knockdown. Mechanistically, RNF125 promoted HDAC1 ubiquitination, leading to its proteasomal degradation. Moreover, HDAC1 reduced PGM5 expression by inhibiting H3K27ac enrichment at the PGM5 promoter.

CONCLUSION

RNF125 suppressed EMT and glycolysis in BC cells and delayed tumor growth in subcutaneous tumor-bearing mouse models, as well as lung metastasis in mice through modulation of the HDAC1/PGM5 axis.