Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou (Affiliated Chenzhou Hospital, Southern Medical University), Chenzhou, Hunan, 423000, P.R. China.
Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, 423000, P.R. China.
Mol Med. 2024 Oct 10;30(1):172. doi: 10.1186/s10020-024-00941-5.
The role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/β-catenin pathway.
The expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect β-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR).
In both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced β-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with β-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression.
ELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating β-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-β-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.
ELAVL1 在各种肿瘤的进展中发挥作用。我们的研究旨在探讨 ELAVL1 通过 HMGB3/β-catenin 通路如何控制鼻咽癌细胞的糖酵解过程。
检测临床肿瘤样本和鼻咽癌细胞系中 ELAVL1 的表达。在裸鼠中建立皮下肿瘤模型，研究 ELAVL1 在肿瘤进展中的作用。通过 RNA 下拉和 RIP 实验验证 HMGB3 与 ELAVL1 的关系。TOPFlash/FOPFlash 报告基因检测试剂盒检测 β-catenin 活性。试剂盒检测鼻咽癌细胞的葡萄糖消耗、乳酸生成和 G6PD 活性。Western blot 检测糖酵解相关蛋白的表达。通过细胞外酸化率 (ECAR) 分析糖酵解能力。
在临床样本和鼻咽癌细胞系中，ELAVL1 mRNA 和蛋白的表达水平均上调。ELAVL1 敲低显著抑制鼻咽癌细胞的体内增殖，并抑制鼻咽癌细胞的糖酵解能力。ELAVL1 与 HMGB3 相互作用，导致 HMGB3 mRNA 稳定性增加。HMGB3 过表达升高了 sh-ELAVL1 引起的 β-catenin 活性降低，并逆转了 sh-ELAVL1 对细胞糖酵解能力的抑制作用。β-catenin 抑制剂 (FH535) 处理有效抑制了 HMGB3 过表达诱导的糖酵解能力的促进。
ELAVL1 通过与 HMGB3 相互作用稳定 HMGB3 mRNA，从而激活 β-catenin 通路，促进鼻咽癌细胞的糖酵解。因此，靶向 ELAVL1-HMGB3-β-catenin 轴可能是治疗鼻咽癌的新方法。
