Chujan Suthipong, Vajeethaveesin Nutsira, Satayavivad Jutamaad, Kitkumthorn Nakarin
Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand.
Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Permanent Secretary (OPS), Ministry of Higher Education, Science, Research and Innovation (MHESI), Bangkok, Thailand.
Bioinform Biol Insights. 2024 May 28;18:11779322241256459. doi: 10.1177/11779322241256459. eCollection 2024.
Ameloblastoma (AM) is a benign tumor locally originated from odontogenic epithelium that is commonly found in the jaw. This tumor makes aggressive invasions and has a high recurrence rate. This study aimed to investigate the differentially expressed genes (DEGs), biological function alterations, disease targets, and existing drugs for AM using bioinformatics analysis.
The data set of AM was retrieved from the GEO database (GSE132474) and identified the DEGs using bioinformatics analysis. The biological alteration analysis was applied to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis and hub gene identification were screened through NetworkAnalyst. The transcription factor-protein network was constructed via OmicsNet. We also identified candidate compounds from L1000CDS2 database. The target of AM and candidate compounds were verified using docking simulation.
Totally, 611 DEGs were identified. The biological function enrichment analysis revealed glycosaminoglycan and GABA (γ-aminobutyric acid) signaling were most significantly up-regulated and down-regulated in AM, respectively. Subsequently, hub genes and transcription factors were screened via the network and showed FOS protein was found in both networks. Furthermore, we evaluated FOS protein to be a therapeutic target in AMs. Candidate compounds were screened and verified using docking simulation. Tanespimycin showed the greatest affinity binding value to bind FOS protein.
This study presented the underlying molecular mechanisms of disease pathogenesis, biological alteration, and important pathways of AMs and provided a candidate compound, Tanespimycin, targeting FOS protein for the treatment of AMs.
成釉细胞瘤（AM）是一种局部起源于牙源性上皮的良性肿瘤，常见于颌骨。该肿瘤具有侵袭性，复发率高。本研究旨在通过生物信息学分析，研究成釉细胞瘤的差异表达基因（DEGs）、生物学功能改变、疾病靶点及现有药物。
从基因表达综合数据库（GEO数据库，GSE132474）中检索成釉细胞瘤数据集，并通过生物信息学分析鉴定差异表达基因。将生物学改变分析应用于基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路。通过网络分析软件（NetworkAnalyst）进行蛋白质-蛋白质相互作用（PPI）网络分析和枢纽基因鉴定。通过OmicsNet构建转录因子-蛋白质网络。我们还从L1000CDS2数据库中鉴定候选化合物。使用对接模拟验证成釉细胞瘤的靶点和候选化合物。
共鉴定出611个差异表达基因。生物学功能富集分析显示，氨基聚糖和GABA（γ-氨基丁酸）信号在成釉细胞瘤中分别显著上调和下调。随后，通过网络筛选出枢纽基因和转录因子，结果显示FOS蛋白在两个网络中均有发现。此外，我们评估FOS蛋白是成釉细胞瘤的治疗靶点。通过对接模拟筛选并验证了候选化合物。坦西莫司显示出与FOS蛋白结合的最大亲和力结合值。
本研究揭示了成釉细胞瘤疾病发病机制、生物学改变及重要通路的潜在分子机制，并提供了一种靶向FOS蛋白的候选化合物坦西莫司用于治疗成釉细胞瘤。
