Abnormal glucose metabolism is a highlight of tumor metabolic reprogramming and is closely related to the development of malignancies. p52-ZER6, a C₂H₂-type zinc finger protein, promotes cell proliferation and tumorigenesis. However, its role in the regulation of biological and pathological functions remains poorly understood. Here, we examined the role of p52-ZER6 in tumor cell metabolic reprogramming. Specifically, we demonstrated that p52-ZER6 promotes tumor glucose metabolic reprogramming by positively regulating the transcription of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway (PPP). By activating the PPP, p52-ZER6 was found to enhance the production of nucleotides and nicotinamide adenine dinucleotide phosphate, thereby providing tumor cells with the building blocks of ribonucleic acids and cellular reductants for reactive oxygen species scavenging, which subsequently promotes tumor cell proliferation and viability. Importantly, p52-ZER6 promoted PPP-mediated tumorigenesis in a p53-independent manner. Taken together, these findings reveal a novel role for p52-ZER6 in regulating G6PD transcription via a p53-independent process, ultimately resulting in tumor cell metabolic reprogramming and tumorigenesis. Our results suggest that p52-ZER6 is a potential target for the diagnosis and treatment of tumors and metabolic disorders.

糖代谢异常是肿瘤代谢重编程的一个亮点，与恶性肿瘤的发生发展密切相关。p52-ZER6 是一种 C ₂ H ₂型锌指蛋白，可促进细胞增殖和肿瘤发生。然而，其在调节生物学和病理学功能中的作用仍然知之甚少。在这里，我们检查了 p52-ZER6 在肿瘤细胞代谢重编程中的作用。具体而言，我们证明 p52-ZER6 通过正向调节葡萄糖-6-磷酸脱氢酶( G6PD)的转录来促进肿瘤葡萄糖代谢重编程), 磷酸戊糖途径 (PPP) 中的限速酶。通过激活 PPP，p52-ZER6 被发现可以增强核苷酸和烟酰胺腺嘌呤二核苷酸磷酸的产生，从而为肿瘤细胞提供核糖核酸和活性氧清除所需的细胞还原剂，从而促进肿瘤细胞增殖和活力. 重要的是，p52-ZER6 以不依赖 p53 的方式促进了 PPP 介导的肿瘤发生。总之，这些发现揭示了 p52-ZER6 在通过 p53 独立过程调节G6PD转录中的新作用，最终导致肿瘤细胞代谢重编程和肿瘤发生。我们的结果表明p52-ZER6是诊断和治疗肿瘤和代谢紊乱的潜在靶点。