Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, Guangdong 515041, P.R. China.
Department of Rheumatology, First Affiliated Hospital of Shantou University Medical College, Guangdong 515041, P.R. China.
Biosci Rep. 2022 Nov 30;42(11). doi: 10.1042/BSR20221311.
Methylation of N6 adenosine (m6A) plays a crucial role in the development and progression of cancers. Its modification is regulated by three types of m6A-related regulators (methyltransferases (writers), demethylases (erasers), and RNA-binding proteins (readers)). Till now, the functions and roles of these regulators in head and neck squamous cell carcinoma (HNSC) remain largely unexplored. Therefore, we utilized the open HNSC dataset in The Cancer Genome Atlas (TCGA), four different cell lines, and our HNSC patient samples (n=40) to explore the clinical significance of 19 m6A regulators, and selected the most significant prognosis-related regulator. Authentic analyses based on online websites were also used in the study (Oncomine, UALCAN, Kaplan-Meier plotter, Human Protein Atlas (HPA), cBioPortal, LinkedOmics, String, etc.). From the results, general overexpression of m6A regulators was observed in pan-cancer, especially in HNSC. IGF2BP2 was recognized as the hub m6A regulator, which was an independent, unfavorable prognostic factor in HNSC. Its mRNA and protein expression in HNSC were significantly up-regulated. Gene mutation types of IGF2BP2 in HNSC (32%) were mainly mRNA High or Amplification, which represented the high expression of IGF2BP2. And these mutations were associated with a poor prognosis. In functional analysis, IGF2BP2 was negatively correlated to tumor immune infiltration in HNSC. Finally, HMGA2 might interact with the IGF2BP2 in HNSC. In conclusion, IGF2BP2 serves as a core m6A regulator among all regulators in HNSC, which has a high expression and predicts the poor prognosis of HNSC patients independently. IGF2BP2 might bring a new direction for HNSC treatment in the future.
N6 腺苷甲基化（m6A）在癌症的发生和发展中起着至关重要的作用。其修饰受三种类型的 m6A 相关调节剂（甲基转移酶（writer）、去甲基化酶（eraser）和 RNA 结合蛋白（reader））调控。到目前为止，这些调节剂在头颈部鳞状细胞癌（HNSC）中的功能和作用在很大程度上仍未被探索。因此，我们利用癌症基因组图谱（TCGA）中的公开 HNSC 数据集、四种不同的细胞系和我们的 HNSC 患者样本（n=40）来探索 19 种 m6A 调节剂的临床意义，并选择了最显著的与预后相关的调节剂。该研究还使用了基于在线网站的真实分析（Oncomine、UALCAN、Kaplan-Meier plotter、Human Protein Atlas（HPA）、cBioPortal、LinkedOmics、String 等）。结果表明，m6A 调节剂在泛癌中普遍过表达，尤其是在 HNSC 中。IGF2BP2 被认为是枢纽 m6A 调节剂，在 HNSC 中是独立的、不利的预后因素。其在 HNSC 中的 mRNA 和蛋白表达显著上调。HNSC 中 IGF2BP2 的基因突变类型（32%）主要为 mRNA 高或扩增，代表 IGF2BP2 的高表达。这些突变与预后不良相关。在功能分析中，IGF2BP2 与 HNSC 中的肿瘤免疫浸润呈负相关。最后，HMGA2 可能与 HNSC 中的 IGF2BP2 相互作用。总之，IGF2BP2 是 HNSC 中所有调节剂的核心 m6A 调节剂，其高表达可独立预测 HNSC 患者的不良预后。IGF2BP2 可能为未来 HNSC 的治疗带来新方向。
