高恶性、早转移、死亡率高的黑色素瘤，其发病机制尚未阐明。研究表明代谢重编程贯穿于肿瘤发生发展进程中，有望成为肿瘤新治疗靶标。我们发现呼吸链复合体I的核心亚基NDUFS3在黑色素瘤组织和细胞高表达，可能与患者生存及不良预后相关，对此无相关报道。结合研究进展，提出假说：高表达NDUFS3调控黑色素瘤细胞的增殖与凋亡，其机制依赖“NDUFS3→氧化磷酸化→AMPK→PRPS1→核苷酸代谢重编程”途径。据此，本项目首先确定NDUFS3在黑色素瘤中的表达及其与临床病理特征的相关性；然后用NDUFS3敲低/过表达细胞、激活剂/抑制剂、线粒体功能检测以及动物模型探讨NDUFS3调控黑色素瘤细胞增殖与凋亡的机制；最后通过Co-IP、免疫荧光、LC-MS等技术阐明AMPK靶向PRPS1介导核苷酸代谢重编程。本研究聚焦NDUFS3在代谢重编程中的作用机制，为靶向干预细胞代谢治疗黑色素瘤的新策略提供理论依据。

The molecular pathogenesis of melanoma with high malignancy, early metastasis and high mortality has not yet been elucidated. Studies have shown that metabolic reprogramming occurs throughout the course of tumorigenesis and development, which is a promising new therapeutic target for cancer. Our previous studies have shown that NDUFS3, the core subunit of respiratory chain complex I, was highly expressed in melanoma tissues and cells, which may be related to survival and poor prognosis of patients, but no relevant report. Combining with recent research progresses, it is hypothesized that the highly expressed NDUFS3 mediates the proliferation and apoptosis of melanoma cells, and the mechanism is dependent on the pathway of "NDUFS3→oxidative phosphorylation→AMPK→PRPS1→nucleotide metabolism reprogramming. To test this hypothesis, we will firstly determine the expression of NDUFS3 in melanoma and its correlation with clinicopathological features and prognosis in clinical samples. Secondly, we want to verify the role of NDUFS3 regulated proliferation and apoptosis in melanoma by NDUFS3 knockdown/overexpression cells, activator/inhibitor, mitochondrial function detection, and animal models. Finally, we attempt to elucidate the molecular mechanism of AMPK targeting PRPS1 mediated nucleotide reprogramming by Co-IP, immunofluorescence, LC-MS and other techniques. Taken together, our study is designed to focus on the molecular mechanism of NDUFS3 in metabolic reprogramming, which provides a theoretical basis for the targeted intervention of cell metabolism in new strategies for melanoma treatment.