PDF(Pubmed)
Abstract：
Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415. The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00223-2.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00223-2.
摘要：
成釉细胞瘤是一种非癌性但侵袭性的口腔肿瘤，从牙源性上皮组织中出现，涉及牙源性牙齿发育。由于缺乏揭示成釉细胞瘤的完整分子发病机制，化疗尝试较少,对最佳治疗方案存在很多分歧.因此，直到日期，广泛的手术切除被认为是成釉细胞瘤的可靠治疗方法。神经营养蛋白信号通路在神经元信号中起着重要作用,与MAPK通路密切相关,另一方面调节细胞分化，凋亡，扩散,可塑性和生存。蛋白质-蛋白质相互作用分析用STRING工具使用WNL值进行分析。确定CTNNB1，HRAS，NGFR,NGFR,和SORT1与BDNF高度相互作用，NT4,p75NTR,NGF,NT3本体论分析结果显示神经营养因子信号通路与细胞表面受体信号通路有关,细胞分化的调节，发展过程的调节，EGFR酪氨酸激酶抑制剂耐药,MAPK信号通路,PI3K-Akt信号通路和Ras信号通路导致发病涉及基因。Further,蛋白质BDNF的聚类系数值，NT4,p75NTR,NGF&NT3鉴定为0.627、0.708、0.367、0.644&0.415。分子对接研究的结果表明，在选定的配体中，甲基--柱酸，N-(4-羟基-苯基)-2-苯基-N-苯基乙酰基-乙酰胺,Atranorin和Oresellinate表现出与所选蛋白质的高结合亲和力。揭示了神经营养蛋白信号通路导致成釉细胞瘤发病的关键基因，它们与细胞分化密切相关，细胞增殖，促凋亡，和支持生存的法规。进一步可以得出结论，神经营养蛋白信号通路可能是为成釉细胞瘤治疗定制靶向药物治疗的有希望的通路之一。
■在线版本包含补充材料，可在10.1007/s40203-024-00223-2获得。
■在线版本包含补充材料，可在10.1007/s40203-024-00223-2获得。
