Zhang Limei, Li Dailin, Zheng Xu, Wu Moli, Yao Qijun, Chen Haoran, Ye Zhiqiang, Yuan Bo
Department of Reparative and Reconstructive Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Neurology Department, Central Hospital of Dalian University of Technology, Dalian, Liaoning, China.
Front Genet. 2025 Feb 24;16:1526018. doi: 10.3389/fgene.2025.1526018. eCollection 2025.
Melanoma, a highly aggressive form of skin cancer, and Parkinson's disease (PD), a progressive neurodegenerative disorder, have been epidemiologically linked, showing a positive association that suggests a shared etiology. This association implies that individuals with one condition may have an increased risk of developing the other. However, the specific molecular mechanisms underlying this relationship remain unclear. This study aimed to elucidate the molecular mechanisms by conducting a comprehensive comparative analysis of gene expression profiles in both PD and melanoma to identify common differentially expressed genes (DEGs) that may contribute to the pathophysiological overlap between these two conditions.
We analyzed two independent publicly available genomic datasets to identify overlapping DEGs associated with both PD and melanoma. Regulatory networks, including transcription factors (TFs), DEGs, and microRNAs (miRNAs), were constructed. Protein-protein interaction (PPI) networks were established to identify hub genes. Additionally, we investigated the interplay between PD, melanoma, and immune cell infiltration to uncover potential correlations between the expression levels of hub genes and specific subsets of immune cells. Molecular docking studies were performed to identify potential therapeutic agents targeting the DEGs.
A total of 41 overlapping DEGs were identified, including VSNL1, ATP6V1G2, and DNM1, which were significantly down-regulated in both PD and melanoma patients. These genes play critical roles in biological processes, cellular components, and molecular functions relevant to the pathogenesis of both diseases. VSNL1 is associated with synaptic vesicle fusion and may impact neuronal communication compromised in PD. ATP6V1G2, a subunit of the V-ATPase, is involved in the dysregulated pH homeostasis observed in melanoma. DNM1, a key player in vesicle trafficking, may influence aberrant cellular transport processes in both diseases. Regulatory and PPI networks revealed potential hub genes and their interactions. Molecular docking studies identified retinoic acid as a potential therapeutic agent targeting VSNL1, ATP6V1G2, and DNM1.
Our study provides insights into the shared molecular characteristics of PD and melanoma, identifying potential biomarkers for early diagnosis and prognosis and revealing new therapeutic targets. The discovery of retinoic acid as a promising therapeutic agent represents a significant step forward in drug development and treatment strategies for these diseases. This comprehensive analysis enhances our understanding of the intricate molecular mechanisms underlying the association between PD and melanoma, paving the way for further research and therapeutic advancements. The findings hold the promise of improved diagnosis, prognosis, and personalized treatment strategies for individuals affected by these debilitating diseases.
黑色素瘤是一种侵袭性很强的皮肤癌,而帕金森病(PD)是一种进行性神经退行性疾病,它们在流行病学上存在关联,呈现出正相关关系,这表明两者有共同的病因。这种关联意味着患有一种疾病的个体患另一种疾病的风险可能会增加。然而,这种关系背后的具体分子机制仍不清楚。本研究旨在通过对PD和黑色素瘤的基因表达谱进行全面的比较分析,以阐明分子机制,从而识别出可能导致这两种疾病病理生理重叠的共同差异表达基因(DEG)。
我们分析了两个独立的公开基因组数据集,以识别与PD和黑色素瘤相关的重叠DEG。构建了包括转录因子(TF)、DEG和微小RNA(miRNA)在内的调控网络。建立了蛋白质-蛋白质相互作用(PPI)网络以识别枢纽基因。此外,我们研究了PD、黑色素瘤和免疫细胞浸润之间的相互作用,以揭示枢纽基因表达水平与免疫细胞特定亚群之间的潜在相关性。进行了分子对接研究,以识别靶向DEG的潜在治疗药物。
共鉴定出41个重叠DEG,包括VSNL1、ATP6V1G2和DNM1,它们在PD和黑色素瘤患者中均显著下调。这些基因在与两种疾病发病机制相关的生物过程、细胞成分和分子功能中发挥关键作用。VSNL1与突触小泡融合相关,可能影响PD中受损的神经元通讯。ATP6V1G2是V-ATP酶的一个亚基,参与黑色素瘤中观察到的pH稳态失调。DNM1是囊泡运输中的关键因子,可能影响两种疾病中异常的细胞运输过程。调控网络和PPI网络揭示了潜在的枢纽基因及其相互作用。分子对接研究确定视黄酸是一种靶向VSNL1、ATP6V1G2和DNM1的潜在治疗药物。
我们的研究深入了解了PD和黑色素瘤的共同分子特征,识别出了早期诊断和预后的潜在生物标志物,并揭示了新的治疗靶点。视黄酸作为一种有前景的治疗药物的发现,代表了这些疾病药物开发和治疗策略向前迈出的重要一步。这种全面分析增强了我们对PD和黑色素瘤之间关联背后复杂分子机制的理解,为进一步研究和治疗进展铺平了道路。这些发现有望改善受这些致残性疾病影响个体的诊断、预后和个性化治疗策略。