Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Pharmacy, Huang Dao District Second Hospital of Traditional Chinese Medicine, Qingdao, China.
BMC Oral Health. 2021 Oct 14;21(1):524. doi: 10.1186/s12903-021-01776-w.
The recurrent aphthous stomatitis (RAS) frequently affects patient quality of life as a result of long lasting and recurrent episodes of burning pain. However, there were temporarily few available effective medical therapies currently. Drug target identification was the first step in drug discovery, was usually finding the best interaction mode between the potential target candidates and probe small molecules. Therefore, elucidating the molecular mechanism of RAS pathogenesis and exploring the potential molecular targets of medical therapies for RAS was of vital importance.
Bioinformatics data mining techniques were applied to explore potential novel targets, weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of the gene chip data from GSE37265, and the hub genes were identified by the Molecular Complex Detection (MCODE) plugin.
A total of 16 co-expression modules were identified, and 30 hub genes in the turquoise module were identified. In addition, functional analysis of Hub genes in modules of interest was performed, which indicated that such hub genes were mainly involved in pathways related to immune response, virus infection, epithelial cell, signal transduction. Two clusters (highly interconnected regions) were determined in the network, with score = 17.647 and 10, respectively, cluster 1 and cluster 2 are linked by STAT1 and ICAM1, it is speculated that STAT1 may be a primary gene of RAS. Finally, genistein, daidzein, kaempferol, resveratrol, rosmarinic acid, triptolide, quercetin and (-)-epigallocatechin-3-gallate were selected from the TCMSP database, and both of them is the STAT-1 inhibitor. The results of reverse molecular docking suggest that in addition to triptolide, (-)-Epigallocatechin-3-gallate and resveratrol, the other 5 compounds (flavonoids) with similar structures may bind to the same position of STAT1 protein with different docking score.
Our study identified STAT1 as the potential biomarkers that might contribute to the diagnosis and potential therapeutic target of RAS, and we can also screen RAS therapeutic drugs from STAT-1 inhibitors.
复发性阿弗他口炎（RAS）常因反复发作的灼痛而长期影响患者的生活质量。然而，目前暂时缺乏有效的医学治疗方法。药物靶点的鉴定是药物发现的第一步，通常是找到潜在的靶候选物和探针小分子之间的最佳相互作用模式。因此，阐明 RAS 发病机制的分子机制，探索 RAS 医学治疗的潜在分子靶点至关重要。
应用生物信息学数据挖掘技术探索潜在的新靶点，采用加权基因共表达网络分析（WGCNA）对 GSE37265 基因芯片数据构建共表达模块，利用分子复合物检测（MCODE）插件识别枢纽基因。
共鉴定出 16 个共表达模块，鉴定出绿松石模块中的 30 个枢纽基因。此外，对感兴趣模块中的枢纽基因进行功能分析，表明这些枢纽基因主要参与与免疫反应、病毒感染、上皮细胞、信号转导相关的途径。网络中确定了两个簇（高度相互连接的区域），分别为分数=17.647 和 10，簇 1 和簇 2 通过 STAT1 和 ICAM1 连接，推测 STAT1 可能是 RAS 的主要基因。最后，从 TCMSP 数据库中选择染料木黄酮、大豆苷元、山奈酚、白藜芦醇、迷迭香酸、雷公藤甲素、槲皮素和（-）-表没食子儿茶素-3-没食子酸酯，它们都是 STAT-1 抑制剂。反向分子对接结果表明，除雷公藤甲素外，（-）-表没食子儿茶素-3-没食子酸酯和白藜芦醇，其他 5 种（黄酮类化合物）结构相似的化合物可能与 STAT1 蛋白的相同位置结合，但结合得分不同。
本研究鉴定了 STAT1 作为潜在的生物标志物，可能有助于 RAS 的诊断和潜在的治疗靶点，我们还可以从 STAT-1 抑制剂中筛选 RAS 治疗药物。
