Table_2_IGF2BP2 promotes head and neck squamous carcinoma cell proliferation and growth via the miR-98-5p/PI3K/Akt signaling pathway.docx

IntroductionAs a N6-methyladenosine reader protein, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a critical player in tumor progression and metastasis. However, its specific function in head and neck squamous carcinoma (HNSCC) has yet to be determined. The present study aimed to determine the role of IGF2BP2 in HNSCC.
MethodsThe expression of IGF2BP2 in HNSCC was analyzed using The Cancer Genome Atlas (TCGA) dataset and detected in HNSCC tissues and cells, respectively. Gain- and loss- of function methods were employed to study the effects of IGF2BP2 on HNSCC cell proliferation and tumorigenesis in vitro and in vivo. MicroRNAs (miRNAs) regulating IGF2BP2 were predicted using online tools and confirmed experimentally.
ResultsWe showed augmented IGF2BP2 expression in HNSCC, which correlated with poor clinical outcomes. Functional studies showed that IGF2BP2 promoted HNSCC cell proliferation by facilitating cell cycle progression while inhibiting apoptosis. We further demonstrated that IGF2BP2 could enhance HNSCC cell tumorigenesis in vivo. Mechanistically, our data revealed that miR-98-5p could directly target IGF2BP2. The interplay between IGF2BP2 and miR-98-5p is essential to drive the progression of HNSCC via the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) pathway signaling pathway.
DiscussionThe current study revealed the oncogenic role of IGF2BP2 and provided insights into its potential mechanism in HNSCC tumorigenesis. Additionally, IGF2BP2 might represent a promising therapeutic target and serve as prognostic biomarker in patients with HNSCC.

引言
作为一种N6-甲基腺苷（N6-methyladenosine）阅读蛋白，胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）在肿瘤进展与转移过程中发挥关键作用。然而，其在头颈部鳞状细胞癌（HNSCC）中的具体功能尚未明确。本研究旨在阐明IGF2BP2在HNSCC中的作用。
方法
本研究利用癌症基因组图谱（TCGA）数据集分析HNSCC组织中IGF2BP2的表达水平，并分别在HNSCC临床组织与细胞系中对其表达进行检测。采用功能获得与功能缺失实验方法，体外及体内探究IGF2BP2对HNSCC细胞增殖及致瘤性的影响。通过在线工具预测靶向调控IGF2BP2的微小RNA（miRNAs），并经实验验证其靶向关系。
结果
本研究发现HNSCC组织中IGF2BP2表达上调，且其表达水平与不良临床预后显著相关。功能实验表明，IGF2BP2通过促进细胞周期进程并抑制细胞凋亡，从而增强HNSCC细胞的增殖能力。进一步体内实验证实，IGF2BP2可提升HNSCC细胞的体内致瘤性。机制研究显示，miR-98-5p可直接靶向结合IGF2BP2；IGF2BP2与miR-98-5p的相互作用，通过磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）-蛋白激酶B（Akt）信号通路，是驱动HNSCC进展的关键环节。
讨论
本研究阐明了IGF2BP2的致癌功能，并揭示了其在HNSCC发生发展中的潜在作用机制。此外，IGF2BP2有望成为HNSCC患者潜在的治疗靶点与预后生物标志物。