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Abstract：
DPP3, a dipeptidyl peptidase, participates in a variety of pathophysiological processes. DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies. However, its specific role and molecular mechanism are still unknown. In this study, the expression of DPP3 in breast cancer tissues is analyzed using TCGA database. Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes. To explore the biological function and mechanisms of DPP3 in breast cancer, biochemical and cell biology assays are conducted in vitro. DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples. Patients with high expression of DPP3 have poor survival outcomes. The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited, and apoptosis is increased in vitro. GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors. Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells. The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids. This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients. These findings will provide a new therapeutic target for the treatment of breast cancer.
摘要：
DPP3，一种二肽基肽酶，参与多种病理生理过程。DPP3在癌症中上调，可能是各种恶性肿瘤发生和发展的关键因素。然而,其具体作用和分子机制尚不清楚。在这项研究中,使用TCGA数据库分析乳腺癌组织中DPP3的表达。进行Kaplan-Meier生存分析以估计DPP3对生存结果的影响。探讨DPP3在乳腺癌中的生物学功能和作用机制,生物化学和细胞生物学测定在体外进行。在TCGA数据库和临床样品中,DPP3在乳腺癌组织中的表达水平高于在邻近组织中的表达水平。DPP3高表达的患者生存结果较差。DPP3基因敲除稳定的乳腺癌细胞系中肿瘤细胞的增殖和迁移能力受到显著抑制,细胞凋亡在体外增加。GSEA分析显示DPP3可影响肿瘤的脂质代谢和脂肪酸合成。随后的实验表明，DPP3可以稳定FASN的表达，从而促进肿瘤细胞中脂肪酸的合成。代谢组学分析的结果还证实DPP3可以影响游离脂肪酸的含量。这项研究表明，DPP3在肿瘤中脂肪酸代谢的重编程中起作用，并且与乳腺癌患者的不良预后有关。这些发现将为乳腺癌的治疗提供新的治疗靶点。
