锌指 E-box 结合同源盒 1 介导有氧糖酵解抑制胰腺癌细胞中的沉默调节蛋白 3。
Zinc finger E-box-binding homeobox 1 mediates aerobic glycolysis suppression of sirtuin 3 in pancreatic cancer.
机构信息
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
出版信息
World J Gastroenterol. 2018 Nov 21;24(43):4893-4905. doi: 10.3748/wjg.v24.i43.4893.
AIM
To uncover the roles of tumor-promoting gene in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.
METHODS
Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced using a lentivirus-mediated method, and the impact of ZEB1 and methyl-CpG binding domain protein 1 (MBD1) on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 (SIRT3) expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatin-immunoprecipitation assays.
RESULTS
ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.
CONCLUSION
ZEB1 silenced SIRT3 expression interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.
目的
揭示肿瘤促进基因在有氧糖酵解调控中的作用，并阐明其潜在的分子机制。
方法
采用慢病毒介导的方法沉默内源性锌指 E 盒结合同源盒 1（ZEB1），使用 Seahorse 细胞通量分析仪、活性氧（ROS）定量和线粒体膜电位测量来检测 ZEB1 和甲基-CpG 结合域蛋白 1（MBD1）对有氧糖酵解的影响。通过共免疫沉淀和免疫荧光测定评估 ZEB1 和 MBD1 之间的相互作用。通过定量聚合酶链反应、Western blot、双荧光素酶和染色质免疫沉淀测定证实了 ZEB1 和 MBD1 相互作用对 SIRT3 表达的影响。
结果
ZEB1 是胰腺癌中有氧糖酵解的正向调节因子。ZEB1 通过与 MBD1 相互作用，转录沉默了线粒体定位的肿瘤抑制因子 SIRT3 的表达。
结论
ZEB1 通过与 MBD1 的相互作用抑制 SIRT3 的表达，从而促进胰腺癌中的有氧糖酵解。
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