PLCε promotes urinary bladder cancer cells proliferation through STAT3/LDHA pathway-mediated glycolysis
PLCε promotes urinary bladder cancer cells proliferation through STAT3/LDHA pathway-mediated glycolysis
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DOI：
10.3892/or.2019.7056
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发表时间：
2019-05-01
期刊：
影响因子：
4.2
通讯作者：
Wu, Xiaohou
中科院分区：
文献类型：
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作者：
Cheng, Honglin;Hao, Yanni;Wu, Xiaohou
磷脂酶C β（PLC β）和无氧糖酵解被确定参与人膀胱癌（UBC）的发展，但其机制尚不清楚。在本研究中，64例膀胱癌和42例癌旁组织标本，从64例患者，和免疫组化表明，PLC β和乳酸脱氢酶（LDHA）在UBC中过表达。研究表明PLC epsilon和LDHA在转录水平上正相关，表明这两个基因中的一个可能受到另一个基因的调节。为了阐明其作用机制，我们用短发夹RNA敲除T24细胞中的PLC β，然后检测到信号转导子和转录激活子3（STAT 3）磷酸化和LDHA的下调，表明PLC β可能通过STAT 3在LDHA的上游发挥作用，调节UBC的糖酵解。此外，进行染色质免疫沉淀和荧光素酶报告基因测定以证实STAT 3可以结合LDHA基因的启动子以增强其表达。异种移植肿瘤小鼠模型也证明了与体外实验相似的结果，进一步证实了PLC在体内调节膀胱细胞生长中的作用。总之，本研究表明，PLC β 1可能通过STAT 3/LDHA途径调节糖酵解，参与人类UBC的发展。
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.