RNF123 inhibits cell viability, cell cycle and colony formation of breast cancer by inhibiting glycolysis via ubiquitination of PFKP

E3 ubiquitin ligases have the potential to modulate key oncogenic pathways. RING finger protein 123 (RNF123), as an E3 ubiquitin ligase, has been functioned as a tumor suppressor. This study was designed to explore the role of RNF123 in breast cancer. Immunohistochemistry was applied to examine protein expression in breast cancer tissues. Western blot and Quantitative Real-time PCR were performed to gauge protein and mRNA levels. Lentivirus transduction was used to overexpress or silence genes of interest. Cell Counting Kit-8, flow cytometry, and colony formation assays were used to assess cell viability, cell cycle, and colony formation. Extracellular acidification rate, lactic acid and adenosine triphosphate were used for glycolysis assay. Co-immunoprecipitation (Co-IP) and ubiquitination analysis were used to explore the interaction between RNF123 and 6-Phosphofructo-2-kinase (PFKP). In vivo experiments were performed with xenograft tumor models. RNF123 was downregulated in tumor tissues and cells, overexpression of which significantly decreased the viability and colony-forming ability of tumor cells, suppressed the progression of the cell cycle and glycolytic activity, and suppressed tumor growth in vivo. Co-IP and ubiquitination analysis revealed that there was an interaction between RNF123 and PFKP, and RNF123 could induce ubiquitination of PFKP. PFKP could reverse the effects of RNF123 on tumor cells. RNF123 inhibited cell viability, cell cycle and colony formation of breast cancer cells by inhibiting glycolysis via ubiquitination of PFKP.