Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/225743
Title: Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis
Authors: Cui, Jianzhou 
Karishma Sachaphibulkij 
Wen Shiun Teo 
Hong Meng Lim 
Li Zou 
Choon Nam Ong 
Rudi Alberts 
Jinmiao Chen 
Lina H. K. Lim 
Keywords: 16S rRNA gene sequencing
gut microbiome
metabolic level
epigenetic signature
PICRUSt
differentially methylated regions
machine learning
restraint stress
serum metabolites
feces metabolites
WGBS
breast cancer
tumorigenesis
Issue Date: 9-May-2022
Publisher: Ivyspring International Publisher
Citation: Cui, Jianzhou, Karishma Sachaphibulkij, Wen Shiun Teo, Hong Meng Lim, Li Zou, Choon Nam Ong, Rudi Alberts, Jinmiao Chen, Lina H. K. Lim (2022-05-09). Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis. Theranostics 12 (8) : 3794-3817. ScholarBank@NUS Repository.
Abstract: Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases. How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear. Methods: Feces and serum samples from BALB/c ANXA1+/+ and ANXA1-/- mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis. Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes. Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results: We report that chronic stress promotes breast tumor growth via a stress-microbiomemetabolite-epigenetic-oncology (SMMEO) axis. Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress. Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors. Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth. Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation. The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.
Source Title: Theranostics
URI: https://scholarbank.nus.edu.sg/handle/10635/225743
ISSN: 1838-7640
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