Department of Spleen and Stomach Disease, Yubei District Hospital of Traditional Chinese Medicine, Chongqing, 401120, China.
Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China.
Cell Biol Toxicol. 2024 Aug 7;40(1):66. doi: 10.1007/s10565-024-09897-y.
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.
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衍生的细胞外囊泡（LEVs）对 SIRT5/p53 轴的影响，重点关注糖酵解代谢重编程和肠上皮细胞的异常增殖。
从植物乳杆菌中分离 LEVs，并与 Caco-2 细胞共孵育。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鉴定关键靶基因和通路。通过 RT-qPCR、EdU 染色、集落形成、流式细胞术和 Western blot 等各种实验评估基因表达、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，并使用动物模型验证了体内效应。
生物信息学分析表明 SIRT5/p53 轴是 LEVs 调节结直肠癌的关键通路。发现 LEVs 通过下调 SIRT5 抑制结直肠癌细胞增殖和糖酵解代谢，影响 p53 去琥珀酰化。在体内，LEVs 调节了这一轴，减少了小鼠肿瘤的形成。临床样本分析表明，SIRT5 和 p53 琥珀酰化水平与患者预后相关。
植物乳杆菌衍生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。这导致糖酵解代谢重编程减少和肠上皮细胞增殖减少。
