2026-10-06T21:38:22Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34024095 2026-09-29T13:58:00Z category_24691 item_type_1 month_year_09_2026

<b>Integrative Multi-Omics Analysis Identifies a Candidate Gut Microbiota–Butyrate–JUN Regulatory Axis in Lung Adenocarcinoma</b> Boxuan Qiu (24533893) Medical bacteriology lung adenocarcinoma gut microbiota butyrate Mendelian randomization transcription factor activity Molecular dockig <p dir="ltr">Lung adenocarcinoma (LUAD) is highly heterogeneous, and the mechanisms linking gut microbiota-derived metabolites to tumor-associated transcriptional regulation remain unclear. We integrated two paired LUAD transcriptomic datasets, GSE40419 and GSE32863, to perform differential expression, functional enrichment, protein-protein interaction (PPI), and transcription factor (TF) activity analyses. Candidate microbial metabolites and targets were obtained from gutMGene, Similarity Ensemble Approach (SEA), and SwissTargetPrediction (STP), while Mendelian randomization (MR) was used to evaluate associations between genetically predicted gut microbial abundance and LUAD risk. Molecular docking and a 100-ns molecular dynamics simulation were conducted to assess interactions between candidate metabolites and JUN-containing DNA-bound complexes. We identified 1,271 and 2,519 differentially expressed genes in GSE40419 and GSE32863, respectively, including 912 overlapping genes. These genes were mainly enriched in cell-cycle, immune and inflammatory, angiogenic, and tumor microenvironment-related pathways. Fifteen robust transcription factors were identified, with consistent suppression of the JUN-regulated transcriptional program. MR analysis identified 10 microbial taxa associated with LUAD after false-discovery-rate correction. Genetically predicted higher abundance of Roseburia inulinivorans was associated with lower LUAD risk (OR = 0.843, 95% CI: 0.756-0.940). Database integration linked R. inulinivorans to butyrate and JUN. Butyrate showed the most favorable docking score with the c-Jun-DNA complex (-4.5 kcal/mol), and molecular dynamics simulation indicated a relatively stable interaction. Collectively, these findings support a putative R. inulinivorans-butyrate-JUN regulatory axis linking gut microbial metabolism to transcriptional dysregulation in LUAD.</p> 2026-09-29T13:58:00Z Image Figure 10.6084/m9.figshare.34024095.v1 https://figshare.com/articles/figure/_b_Integrative_Multi-Omics_Analysis_Identifies_a_Candidate_Gut_Microbiota_Butyrate_JUN_Regulatory_Axis_in_Lung_Adenocarcinoma_b_/34024095 CC BY 4.0