PDF(Pubmed)
Abstract：
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：
头颈部鳞状细胞癌（HNSCC）是全球最常见的癌症之一，每年造成数十万人死亡。不幸的是,大多数患者被诊断为晚期，只有一部分患者对治疗反应良好。为了填补这一空白，我们在此提出了一项回顾性的计算机模拟研究，以阐明驱动HNSCC发展的基因-miRNA相互作用。此外，确定拓扑生物标志物作为设计新药的来源。为了实现这一点，使用蛋白质-蛋白质相互作用(PPI)和双向miRNA-靶网络对患者和对照的基因和miRNA谱进行全面重新评估.细胞骨架重塑，细胞外基质（ECM），免疫系统,蛋白水解，和能量代谢已成为HNSCC发病机理中涉及的主要功能模块。值得注意的是，我们的研究结果的景观描绘了在激活基因促进细胞周期和增殖的协同分子作用，使那些压抑的人失活。在这种情况下，基因，包括VEGFA,EMP1、PPL、KRAS,MET,TP53、MMPs和HOX，和miRNAs，包括mir-6728和mir-99a，成为驱动HNSCC肿瘤发生的分子相互作用的关键参与者。尽管这些HNSCC亚型具有异质性，以及一项研究指向可能与上下文相关的关系的局限性，与先前发表的研究的重叠令人鼓舞.因此，它支持对关键分子的进一步研究，两者都已经与HNSCC无关。
