Yin Changwei, Miao Yi, Lu Wei, Liu Zhenxing
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
Department of Stomatology, The People's Hospital of Huaiyin Jinan, Jinan, Shandong, 250021, China.
Adv Biol (Weinh). 2025 Jul;9(7):e2400564. doi: 10.1002/adbi.202400564. Epub 2025 Mar 24.
The function and molecular biological mechanism of immediate early response 3 (IER3) on the tumorigenesis of oral squamous cell carcinoma (OSCC) are aimed to be explored. The effects of IER3 on the proliferation, apoptosis, and mobility of OSCC cells are first assessed utilizing colony formation, EdU assay, flow cytometry, and transwell assay. The effect of IER3 on the glycolytic ability of OSCC cells is validated by detecting the extracellular acidification rate and oxygen consumption rate. Additionally, glycolysis- and wnt/β-catenin signaling-associated protein expressions are examined by western blot. Besides, a mouse tumor xenograft model is established to evaluate the effect of IER3 on tumor progression. IER3 expression is upregulated in OSCC cells and tissues. IER3 enhanced tumor cells' malignant behaviors and also promoted the glycolysis of OSCC cells. Moreover, IER3 is verified to promote the activation of wnt/β-catenin signaling in OSCC. Besides, rescue experiments further proved that IER3 knockdown can inhibit the malignant biological behavior of OSCC cells through inactivating wnt/β-catenin signaling. In vivo, the downregulation of IER3 is also demonstrated to suppress OSCC progression by inactivating wnt/β-catenin signaling. IER3 facilitated tumor progression and aberrant glycolysis via activating wnt/β-catenin pathway in OSCC.
旨在探究即刻早期反应3（IER3）在口腔鳞状细胞癌（OSCC）肿瘤发生中的作用及分子生物学机制。首先利用集落形成实验、EdU实验、流式细胞术和Transwell实验评估IER3对OSCC细胞增殖、凋亡和迁移能力的影响。通过检测细胞外酸化率和耗氧率验证IER3对OSCC细胞糖酵解能力的影响。此外，通过蛋白质免疫印迹法检测糖酵解和wnt/β-连环蛋白信号相关蛋白的表达。此外，建立小鼠肿瘤异种移植模型以评估IER3对肿瘤进展的影响。IER3在OSCC细胞和组织中表达上调。IER3增强了肿瘤细胞的恶性行为，还促进了OSCC细胞的糖酵解。此外，证实IER3可促进OSCC中wnt/β-连环蛋白信号的激活。此外，挽救实验进一步证明，敲低IER3可通过使wnt/β-连环蛋白信号失活来抑制OSCC细胞的恶性生物学行为。在体内，IER3的下调也被证明可通过使wnt/β-连环蛋白信号失活来抑制OSCC进展。IER3通过激活OSCC中的wnt/β-连环蛋白途径促进肿瘤进展和异常糖酵解。
