Wu Di, Li Mingxia, Wang Mingyang, Yan Zhifeng, Meng Yuanguang
School of Medicine, Nankai University, Tianjin, China.
Department of Obstetrics and Gynecology, The First Affiliated Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Oncol. 2024 Sep 5;14:1442965. doi: 10.3389/fonc.2024.1442965. eCollection 2024.
Despite rapid advances in molecular biology, personalized molecular therapy remains a clinical challenge for endometrial cancer due to its complex and heterogeneous tumor microenvironment.Based on clinical findings, AIB1 is a marker molecule for poor prognosis in endometrial cancer and may serve as a potential therapeutic target. Moreover, it is well known that aerobic glycolysis plays an important role in tumour energy metabolism. It has been previously reported in various hormone-related tumour studies that AIB1 affects glycolysis and promotes tumour development. However, the link between AIB1 and aerobic glycolysis in estrogen-dependent endometrial cancer remains unclear.
We used two endometrial cancer cell lines to validate the high expression of target genes and the effect on the proliferative and invasive capacity of the tumours and verified the pattern of interactions and epigenetic modifications by CHIP and CO-IP techniques. Finally, the conclusions were validated on homozygous mice.
In this study, we investigated the transcriptional co-activation functions of AIB1, including its acetylation by PCAF, binding to the c-myc transcription factor, and recruitment of glycolysis-related gene promoters.
Our findings provide new clues that perturbation of normal homeostatic levels of AIB1 is linked with endometrial cancer. These findings suggest that targeting AIB1-mediated regulation of aerobic glycolysis may offer a novel therapeutic approach for endometrial cancer with high AIB1 expression, opening new avenues for personalized diagnostics and treatment strategies in this disease.
尽管分子生物学取得了快速进展，但由于子宫内膜癌复杂且异质性的肿瘤微环境，个性化分子治疗仍然是一项临床挑战。基于临床研究结果，AIB1是子宫内膜癌预后不良的标志物分子，可能作为潜在的治疗靶点。此外，众所周知，有氧糖酵解在肿瘤能量代谢中起重要作用。此前在各种激素相关肿瘤研究中报道，AIB1影响糖酵解并促进肿瘤发展。然而，在雌激素依赖性子宫内膜癌中，AIB1与有氧糖酵解之间的联系仍不清楚。
我们使用两种子宫内膜癌细胞系来验证靶基因的高表达及其对肿瘤增殖和侵袭能力的影响，并通过CHIP和CO-IP技术验证相互作用模式和表观遗传修饰。最后，在纯合小鼠上验证结论。
在本研究中，我们研究了AIB1的转录共激活功能，包括其被PCAF乙酰化、与c-myc转录因子结合以及募集糖酵解相关基因启动子。
我们的研究结果提供了新的线索表明，AIB1正常稳态水平的扰动与子宫内膜癌有关。这些结果表明，针对AIB1介导的有氧糖酵解调节可能为高AIB1表达的子宫内膜癌提供一种新的治疗方法，为该疾病的个性化诊断和治疗策略开辟新途径。
