Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026
Brominated flame retardants: UQCRC1 and NR3C2 as potential targets in IBD and CRC.
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Wu Jianhai, Li Haoran, Wu Chongying, Wu Yunzi, Yu Huangdao, Chen Zhigang
Аннотация
BACKGROUND: Brominated flame retardants (BFRs) are persistent pollutants with health concerns, yet their molecular mechanisms in the inflammatory bowel disease (IBD) and colorectal cancer (CRC) are unclear.
METHODS: We employed an integrated approach combining computational toxicology, bioinformatics, and molecular docking to identify core molecular targets linking BFR exposure to IBD/CRC. The prognostic and immunological significance of key genes was validated using TCGA data and functional assays in human CRC (HT29) and normal colon epithelial (NCM460) cells.
RESULTS: We identified 12 core targets, notably UQCRC1 and NR3C2, which stably bind BFRs. Low expression of UQCRC1 and NR3C2 predicted poor patient prognosis and exhibited consistent positive correlations with anti-tumor immune cell infiltration. In vitro experiments demonstrated that BFR (TBBPA and HBCD) exposure markedly promoted the proliferation, viability and cell cycle progression of HT29 CRC cells, accompanied by significant downregulation of UQCRC1 and NR3C2 expression. In normal NCM460 colon epithelial cells, BFR treatment induced cytotoxicity, inhibited cell proliferation, triggered the upregulation of pro-inflammatory cytokines, and disrupted intestinal barrier function by suppressing the expression of intestinal tight junction proteins.
CONCLUSION: BFR exposure was accompanied by altered expression of UQCRC1/NR3C2 and phenotypic changes in colon cells. Dysregulation of the two genes was significantly correlated with clinical prognosis and tumor immune microenvironment in IBD and CRC patients.
METHODS: We employed an integrated approach combining computational toxicology, bioinformatics, and molecular docking to identify core molecular targets linking BFR exposure to IBD/CRC. The prognostic and immunological significance of key genes was validated using TCGA data and functional assays in human CRC (HT29) and normal colon epithelial (NCM460) cells.
RESULTS: We identified 12 core targets, notably UQCRC1 and NR3C2, which stably bind BFRs. Low expression of UQCRC1 and NR3C2 predicted poor patient prognosis and exhibited consistent positive correlations with anti-tumor immune cell infiltration. In vitro experiments demonstrated that BFR (TBBPA and HBCD) exposure markedly promoted the proliferation, viability and cell cycle progression of HT29 CRC cells, accompanied by significant downregulation of UQCRC1 and NR3C2 expression. In normal NCM460 colon epithelial cells, BFR treatment induced cytotoxicity, inhibited cell proliferation, triggered the upregulation of pro-inflammatory cytokines, and disrupted intestinal barrier function by suppressing the expression of intestinal tight junction proteins.
CONCLUSION: BFR exposure was accompanied by altered expression of UQCRC1/NR3C2 and phenotypic changes in colon cells. Dysregulation of the two genes was significantly correlated with clinical prognosis and tumor immune microenvironment in IBD and CRC patients.