ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/β-catenin axis.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2024-10-10 DOI:10.1186/s10020-024-00941-5

Yi Cui, Haojie Wen, Jinyong Tang, Jiawen Chen, Juan Zhou, Minghua Hou, Xiaohan Rong, Yuanzhao Lan, Qiong Wu

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引用次数: 0

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

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ELAVL1通过HMGB3/β-catenin轴调节鼻咽癌细胞的糖酵解。

背景：ELAVL1在多种肿瘤进展中的作用已被证实。我们的研究旨在探讨 ELAVL1 如何通过 HMGB3/β-catenin 通路控制鼻咽癌细胞的糖酵解过程：方法：在临床肿瘤样本和鼻咽癌细胞系中检测ELAVL1的表达。建立裸鼠皮下肿瘤模型，研究 ELAVL1 在肿瘤进展中的作用。通过 RNA pull down 和 RIP 试验验证了 HMGB3 和 ELAVL1 之间的关系。TOPFlash/FOPFlash报告实验用于检测β-catenin的活性。检测试剂盒用于测量鼻咽癌细胞的葡萄糖消耗、乳酸生成和 G6PD 活性。通过 Western 印迹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：结果：在临床样本和鼻咽癌细胞系中，ELAVL1 mRNA和蛋白质的表达水平均上调。敲除 ELAVL1 能显著抑制鼻咽癌的体内增殖，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 的稳定性增加。过量表达HMGB3可提高sh-ELAVL1导致的β-catenin活性降低，并逆转sh-ELAVL1对细胞糖酵解能力的抑制作用。β-catenin抑制剂（FH535）能有效抑制HMGB3过表达对糖酵解能力的促进作用：结论：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 轴有可能成为治疗鼻咽癌的一种新方法。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.