PLCε promotes urinary bladder cancer cells proliferation through STAT3/LDHA pathway-mediated glycolysis

Phospholipase C epsilon (PLC epsilon) and anaerobic glycolysis were determined to be involved in the development of human urinary bladder cancer (UBC), but the mechanisms remain unclear. In the present study, 64 bladder cancer specimens and 42 adjacent tissue specimens were obtained from 64 patients, and immunochemistry indicated that PLC epsilon and lactate dehydrogenase (LDHA) are overexpressed in UBC. PLC epsilon and LDHA were demonstrated to be positively correlated at transcription levels, indicating that one of these two genes may be regulated by another. To elucidate the mechanisms, PLC epsilon was knocked down in T24 cells by short hairpin RNA, and then signal transducer and activator of transcription 3 (STAT3) phosphorylation and LDHA were determined to be downregulated, which indicated that PLC epsilon may serve roles upstream of LDHA through STAT3 to regulate glycolysis in UBC. Furthermore, chromatin immunoprecipitation and luciferase reporter assays were performed to confirm that STAT3 could bind to the promoter of the LDHA gene to enhance its expression. A xenograft tumor mouse model also demonstrated similar results as the in vitro experiments, further confirming the role of PLC epsilon in regulating bladder cell growth in vivo. Collectively, the present study demonstrated that PLC epsilon may regulate glycolysis through the STAT3/LDHA pathway to take part in the development of human UBC.