Paramasivam Arumugam, George Rinku, Priyadharsini Jayaseelan Vijayashree
Cellular and Molecular Research Centre, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University Chennai, India.
Department of Oral Oncology, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University Chennai, India.
Am J Cancer Res. 2021 Jul 15;11(7):3688-3697. eCollection 2021.
Genetic alterations in N6-methyladenosine (m6A) regulatory genes are observed in many cancers. Recent studies have shown that newly identified m6A regulatory gene family (IGF2BPs; IGF2BP1, IGF2BP2, and IGF2BP3) were highly expressed in various types of cancer that stabilize and promote translation of multiple oncogenes, resulting in tumor development, survival and drug resistance. However, the oncogenic roles and prognostic values of IGF2BPs in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. In this study, we examined the m6A regulatory genes alteration, their mRNAs expression and the prognostic values in HNSCC. We also analyzed the interaction network and functional enrichment of m6A regulators. Our results showed that m6A regulatory genes were altered in 41% (205/504) of HNSCC patients, of which was amplified in 20% (101/504) of HNSCC patents and positively correlated with its mRNA expression. Importantly, we have validated the expression of in HNSCC and normal tissue samples. Interestingly, we also found that the was frequently co-amplified with the most common oncogenes in HNSCC patients. In addition, this study found that other m6A regulatory genes such as , and were significantly upregulated in HNSCC samples. Moreover, patients with high expression of , and had poor overall survival (OS) than those with low expression. Therefore, it is evident that IGF2BP family plays a key role in the oncogenesis of HNSCC and might serve as novel prognostic biomarkers and potential therapeutic targets in HNSCC.
在许多癌症中都观察到了N6-甲基腺苷（m6A）调控基因的遗传改变。最近的研究表明，新发现的m6A调控基因家族（IGF2BPs；IGF2BP1、IGF2BP2和IGF2BP3）在多种类型的癌症中高度表达，这些癌症能稳定并促进多种癌基因的翻译，从而导致肿瘤发展、存活和耐药。然而，IGF2BPs在头颈部鳞状细胞癌（HNSCC）中的致癌作用和预后价值仍 largely未知。在本研究中，我们检测了HNSCC中m6A调控基因的改变、它们的mRNA表达以及预后价值。我们还分析了m6A调节剂的相互作用网络和功能富集情况。我们的结果表明，41%（205/504）的HNSCC患者中m6A调控基因发生改变，其中20%（101/504）的HNSCC患者中该基因被扩增，且与其mRNA表达呈正相关。重要的是，我们已经验证了其在HNSCC和正常组织样本中的表达。有趣的是，我们还发现该基因在HNSCC患者中经常与最常见的癌基因共同扩增。此外，本研究发现其他m6A调控基因如 、 和 在HNSCC样本中显著上调。而且， 、 和 高表达的患者总生存期（OS）比低表达的患者差。因此，很明显IGF2BP家族在HNSCC的肿瘤发生中起关键作用，可能作为HNSCC新的预后生物标志物和潜在的治疗靶点。 （注：原文中部分基因名称未完整给出，用 表示）
