文章：

差异表达基因、miRNA及网络模型：揭示驱动头颈鳞状细胞癌肿瘤发生的分子相互作用策略

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

原文发布日期：4 September 2023

DOI: 10.3390/cancers15174420

类型: Article

开放获取: 是

英文摘要：

Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene–miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein–protein interaction (PPI) and bipartite miRNA–target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC.

摘要翻译： 

头颈部鳞状细胞癌（HNSCC）是全球最常见的癌症之一，每年导致数十万人死亡。遗憾的是，大多数患者在确诊时已处于晚期，且仅部分患者对治疗反应良好。为填补这一空白，本研究提出一项回顾性计算机模拟分析，旨在揭示驱动HNSCC发展的基因-miRNA相互作用网络，并识别可作为新药设计来源的拓扑生物标志物。为实现这一目标，我们通过蛋白质-蛋白质相互作用网络及双向miRNA-靶基因网络，对患者与对照组的基因及miRNA表达谱进行了系统性重评估。研究发现细胞骨架重塑、细胞外基质、免疫系统、蛋白水解及能量代谢是参与HNSCC发病机制的核心功能模块。值得注意的是，研究结果揭示了促进细胞周期与增殖的基因被激活、抑制性基因被失活的协同分子作用机制。在此过程中，VEGFA、EMP1、PPL、KRAS、MET、TP53、MMPs及HOXs等基因，以及mir-6728和mir-99a等miRNA，成为驱动HNSCC肿瘤发生的关键分子节点。尽管HNSCC亚型存在异质性，且本研究揭示的关联可能受特定背景影响，但与既往研究的重合部分具有积极意义。因此，本研究支持对已发现及未发现的HNSCC关键分子开展进一步探索。

原文链接：

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis