Identification of mitochondria-related action targets of quercetin in melanoma cells

Melanoma is a complex and genetically heterogeneous malignant tumor with high rates of mortality. Although current therapies provide a short-term clinical benefit, they are unable to cure the majority of patients with metastatic melanoma. Therefore, the investigation of pathological mechanisms and the development of new therapy strategies for melanoma are of great significance. Quercetin can effectively inhibit tumor growth in various tumors. However, the exact action mechanisms of quercetin against melanoma have not been comprehensively clarified, which limits its application. Accumulating evidence has suggested that the dysfunction of mitochondria is closely linked to carcinogenesis, and a better understanding of the regulation of mitochondria-related genes will shed light on providing new therapies for melanoma. In this study, we performed RNA-seq from melanoma B16-F1 cells treated with quercetin versus controls and screened for differentially expressed genes (DEGs). GO and KEGG enrichment analyses were performed, and a protein–protein interaction (PPI) network was constructed. Combining the results of RNA-seq, molecular docking, and bioinformatics analysis, we found six mitochondria-related genes, BTG2, CP, LRIG1, CYP1A1, GBP2, and MBNL1, which might be targets of quercetin in melanoma and provide an available targeting therapy strategy for melanoma.

黑色素瘤是一种复杂且具有遗传异质性的恶性肿瘤，死亡率居高不下。尽管当前治疗手段可带来短期临床获益，但无法治愈大多数转移性黑色素瘤患者。因此，探究黑色素瘤的病理机制并开发新型治疗策略具有重要意义。槲皮素(Quercetin)可有效抑制多种肿瘤的生长，但其抗黑色素瘤的确切作用机制尚未得到全面阐明，这限制了其临床应用。越来越多的研究表明，线粒体功能异常与肿瘤发生密切相关；深入解析线粒体相关基因的调控机制，将为黑色素瘤的治疗提供新的思路。本研究以槲皮素处理的黑色素瘤B16-F1细胞与对照组细胞为样本开展RNA测序(RNA-seq)，并筛选差异表达基因(differentially expressed genes, DEGs)，随后进行基因本体(Gene Ontology, GO)与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析，并构建蛋白质相互作用(protein–protein interaction, PPI)网络。结合RNA测序(RNA-seq)、分子对接(molecular docking)及生物信息学分析(bioinformatics analysis)结果，本研究筛选得到BTG2、CP、LRIG1、CYP1A1、GBP2及MBNL1共6个线粒体相关基因，它们可能是槲皮素抗黑色素瘤的作用靶点，可为黑色素瘤的靶向治疗提供可行策略。