Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/225743
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dc.titleAnnexin-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
dc.contributor.authorCui, Jianzhou
dc.contributor.authorKarishma Sachaphibulkij
dc.contributor.authorWen Shiun Teo
dc.contributor.authorHong Meng Lim
dc.contributor.authorLi Zou
dc.contributor.authorChoon Nam Ong
dc.contributor.authorRudi Alberts
dc.contributor.authorJinmiao Chen
dc.contributor.authorLina H. K. Lim
dc.date.accessioned2022-05-19T00:55:49Z
dc.date.available2022-05-19T00:55:49Z
dc.date.issued2022-05-09
dc.identifier.citationCui, 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.
dc.identifier.issn1838-7640
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/225743
dc.description.abstractBackground: 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.
dc.publisherIvyspring International Publisher
dc.sourceElements
dc.subject16S rRNA gene sequencing
dc.subjectgut microbiome
dc.subjectmetabolic level
dc.subjectepigenetic signature
dc.subjectPICRUSt
dc.subjectdifferentially methylated regions
dc.subjectmachine learning
dc.subjectrestraint stress
dc.subjectserum metabolites
dc.subjectfeces metabolites
dc.subjectWGBS
dc.subjectbreast cancer
dc.subjecttumorigenesis
dc.typeArticle
dc.date.updated2022-05-18T09:10:51Z
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.contributor.departmentDEAN'S OFFICE (SSH SCH OF PUBLIC HEALTH)
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.description.sourcetitleTheranostics
dc.description.volume12
dc.description.issue8
dc.description.page3794-3817
dc.published.statePublished
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