结直肠癌的进展涉及复杂的细胞机制。本研究探讨了植物乳杆菌来源的细胞外囊泡 (LEV) 对 SIRT5/p53 轴的影响，重点关注肠上皮细胞的糖酵解代谢重编程和异常增殖。从植物乳杆菌中分离出 LEV，并与 Caco-2 细胞一起孵育。通过RNA测序分析差异基因表达并与TCGA-COAD数据进行比较。使用 PPI 网络和通路富集分析确定了关键靶基因和通路。各种测定，包括 RT-qPCR、EdU 染色、集落形成、流式细胞术和蛋白质印迹，用于评估基因表达、细胞增殖和代谢变化。免疫共沉淀证实了SIRT5和p53之间的相互作用，并采用动物模型来验证体内效果。生物信息学分析表明SIRT5/p53轴是LEVs调节结直肠癌的关键途径。研究发现 LEV 通过下调 SIRT5 影响 p53 脱琥珀酰化来抑制结直肠癌细胞增殖和糖酵解代谢。在体内，LEVs 调节该轴，减少小鼠肿瘤的形成。临床样本分析表明SIRT5和p53琥珀酰化水平与患者预后相关。乳酸菌来源的细胞外囊泡通过调节SIRT5/p53轴在抑制结肠肿瘤形成中发挥关键作用。这会导致糖酵解代谢重编程减少和肠上皮细胞增殖减少。© 2024。作者。

Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells.LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects.Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis.Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.© 2024. The Author(s).