Antitumorigenic potential of <i>Lactobacillus</i>-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation

作者全名："Zhang, Jingbo; Huang, Xiumei; Zhang, Tingting; Gu, Chongqi; Zuo, Wei; Fu, Lijuan; Dong, Yiping; Liu, Hao"

作者地址："[Zhang, Jingbo] Yubei Dist Hosp Tradit Chinese Med, Dept Spleen & Stomach Dis, Chongqing 401120, Peoples R China; [Huang, Xiumei; Zhang, Tingting] Rongchang Dist Peoples Hosp Chongqing, Dept Digest, 3 North Guangchang Rd,Changyuan St, Chongqing 402460, Peoples R China; [Gu, Chongqi; Liu, Hao] Rongchang Dist Peoples Hosp, Dept Pediat, Chongqing 402460, Peoples R China; [Zuo, Wei; Fu, Lijuan] Chongqing Med Univ, Sch Tradit Chinese Med, Dept Herbal Med, Chongqing 400016, Peoples R China; [Zuo, Wei; Fu, Lijuan] Changsha Med Univ, Dept Pharmacol, Academician Workstn, Changsha 410219, Peoples R China; [Dong, Yiping] Army Med Univ, Dept Digital Med, Dept Bioengn & Imaging, Chongqing 400038, Peoples R China"

通信作者："Liu, H (通讯作者)，Rongchang Dist Peoples Hosp, Dept Pediat, Chongqing 402460, Peoples R China."

来源：CELL BIOLOGY AND TOXICOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001286346200002

JCR分区：Q1

影响因子：6.1

年份：2024

卷号：40

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Colorectal cancer; Lactobacillus; Extracellular vesicles; SIRT5; p53; Palmitoylation modification

摘要："Objective 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. Methods 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. Results 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. Conclusion 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."

基金机构：Chongqing Rongchang District People's Hospital 2022 the second batch of medical research Cultivation Fund Project

基金资助正文：No Statement Available