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Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome

  • Authors:
    • Hanna Ham
    • Prakrti Senthil
    • Stephanie C. Tan
    • Robert M. Sargis
    • Gail S. Prins
    • Hua Geng
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA, Department of Medical Education, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA, Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
    Copyright: © Ham et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 27
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    Published online on: December 22, 2025
       https://doi.org/10.3892/br.2025.2100
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Abstract

Polychlorinated biphenyl 153 (PCB153) is one of the most persistent environmental pollutants and abundant PCB congeners detected in human tissues, primarily acquired through dietary exposure. The intestinal epithelium therefore represents a critical initial target for PCB‑related toxicity. However, the molecular mechanisms by which PCB153 disrupts normal intestinal epithelial function remain incompletely understood. The present study investigated the effects of PCB153 exposure on non‑transformed human intestinal epithelial cells (IECs) using transcriptomic profiling. The data revealed that PCB153 induced dose‑dependent alterations in the IEC transcriptome. Key pathways affected by PCB153 included Wnt signaling, ABC transporters, cGMP‑PKG signaling and metallothionein‑mediated metal homeostasis. High‑dose exposure further activated inflammatory and tumorigenic pathways such as TNF and NF‑κB signaling, while suppressing mitochondrial metabolism, oxidative phosphorylation and cellular detoxification processes. To the best of our knowledge, this is the first report that reveals the extensive transcriptomic remodeling in normal human IECs in response to PCB153 exposure, highlighting the disrupted intestinal regeneration, immune response and metabolic regulation. These findings provide novel mechanistic insights into how PCB153 compromises intestinal epithelial health, and establishes a transcriptomic framework for identifying biomarkers and therapeutic targets related to environmental toxicant exposure.
View Figures

Figure 1

Effects of PCB153 on NCM460D cell
viability. NCM460D cells were treated with a series of
concentrations of PCB153 (0, 0.5, 5, 50 and 200 µM) for (A) 6, (B)
24 and (C) 48 h. Cell viability was determined using the
PrestoBlue™ HS assay. Data are presented as the mean ±
SD from six biological repeats. One-way ANOVA with Tukey's post hoc
test; ***P<0.001, ****P<0.0001. OD,
optical density; PCB153, polychlorinated biphenyl 153.

Figure 2

Dose-dependent transcriptomic
alterations in human IECs following PCB153 exposure. (A) PC
analysis of RNA-seq data showing distinct clustering of control and
PCB153-treated IECs, with a clear dose-dependent separation between
the 5 and 50 µM exposure groups. (B) MA plot of DEGs in IECs
treated with 5 µM PCB153 compared with the control group,
highlighting 329 upregulated and 246 downregulated genes (adjusted
P<0.05). (C) MA plot of DEGs in IECs treated with 50 µM PCB153
compared with the control group, showing 4,006 upregulated and
3,070 downregulated genes (adjusted P<0.05). (D) Venn diagram
illustrating the overlap of DEGs between the 5 and 50 µM PCB153
treatment groups, identifying 181 commonly upregulated and 136
commonly downregulated genes, with the top 20 DEGs (ranked by
P-value) visualized in a heatmap. RNA-seq data from two independent
biological experiments, each performed in duplicate are presented.
(E) Reverse transcription-quantitative PCR validation of selected
representative DEGs (MT1G, MT2A, LGR5,
DACT1 and LEF1) confirming induction of
metallothionein genes and suppression of Wnt-related targets,
consistent with RNA-seq results. n=3 for each group. Statistical
significance was determined using one-way ANOVA.
*P<0.05, **P<0.01,
***P<0.001. DEG, differentially expressed gene; IEC,
intestinal epithelial cell; ns, not significant; PC, principal
component; PCB153, polychlorinated biphenyl 153; RNA-seq, RNA
sequencing; MA plot, minus-average plot.

Figure 3

Pathway enrichment analysis of
commonly dysregulated genes in IECs following PCB153 exposure. (A)
KEGG pathway enrichment analysis of 181 commonly upregulated genes
revealed significant enrichment in pathways related to ‘mineral
absorption’, ‘ribosome’, ‘coronavirus disease’ and ‘axon guidance’.
(B) Network analysis of upregulated pathways highlighted potential
interactions between ‘ribosome’ and viral response-related pathways
(‘coronavirus disease’). (C) KEGG pathway enrichment analysis of
136 commonly downregulated genes identified significant suppression
of pathways involved in ‘DNA replication’, ‘ABC transporters’,
digestive secretions (‘gastric acid secretion’, ‘pancreatic
secretion’ and ‘salivary secretion’), ‘cGMP-PKG signaling’, ‘cell
cycle’, ‘estrogen signaling’ and ‘Wnt signaling’. (D) Network
analysis of downregulated pathways showed interconnected
suppression of digestive secretion pathways and the ‘cGMP-PKG
signaling pathway’, indicating impaired intestinal epithelial
physiology. (B and D) Interactive plot shows the relationship
between enriched pathways. Two pathways (nodes) are connected if
they share ≥20% of genes. Darker nodes are more significantly
enriched gene sets. Bigger nodes represent larger gene sets.
Thicker edges represent more overlapped genes. DEG, differentially
expressed gene; FDR, false discovery rate; IEC, intestinal
epithelial cell; KEGG, Kyoto Encyclopedia of Genes and Genomes;
PCB153, polychlorinated biphenyl 153.

Figure 4

Dose-dependent pathway alterations in
IECs following PCB153 exposure. KEGG pathway enrichment analysis of
(A) upregulated genes and (B) downregulated genes in IECs treated
with 5 µM PCB compared with the control group. (C and D) The top 20
enriched pathways in IECs treated with 50 µM PCB153 were ranked by
fold enrichment and reorganized into functional modules (indicated
by the font color) to improve clarity and interpretability. (A-D)
Upregulated pathways were grouped into ‘Immune & Host-Defense’
(magenta), ‘Proteostasis & Translation’ (orange),
‘Proliferation/Oncogenic’ (violet) and ‘Others’ (brown) categories,
whereas downregulated pathways were grouped into ‘Core Energy &
Lipid Metabolism’ (light blue), ‘Genome Maintenance &
Proliferation’ (dark blue), ‘Neurodegeneration & Proteostasis
Stress’ (green) and ‘Transport/Signaling & Global’ (black)
categories. The significance of pathway enrichment is shown as
-log10(FDR), with higher values indicating stronger
statistical enrichment. DEG, differentially expressed gene; FDR,
false discovery rate; IEC, intestinal epithelial cell; KEGG, Kyoto
Encyclopedia of Genes and Genomes; PCB153, polychlorinated biphenyl
153.
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Spandidos Publications style
Ham H, Senthil P, Tan SC, Sargis RM, Prins GS and Geng H: Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome. Biomed Rep 24: 27, 2026.
APA
Ham, H., Senthil, P., Tan, S.C., Sargis, R.M., Prins, G.S., & Geng, H. (2026). Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome. Biomedical Reports, 24, 27. https://doi.org/10.3892/br.2025.2100
MLA
Ham, H., Senthil, P., Tan, S. C., Sargis, R. M., Prins, G. S., Geng, H."Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome". Biomedical Reports 24.2 (2026): 27.
Chicago
Ham, H., Senthil, P., Tan, S. C., Sargis, R. M., Prins, G. S., Geng, H."Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome". Biomedical Reports 24, no. 2 (2026): 27. https://doi.org/10.3892/br.2025.2100
Copy and paste a formatted citation
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Spandidos Publications style
Ham H, Senthil P, Tan SC, Sargis RM, Prins GS and Geng H: Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome. Biomed Rep 24: 27, 2026.
APA
Ham, H., Senthil, P., Tan, S.C., Sargis, R.M., Prins, G.S., & Geng, H. (2026). Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome. Biomedical Reports, 24, 27. https://doi.org/10.3892/br.2025.2100
MLA
Ham, H., Senthil, P., Tan, S. C., Sargis, R. M., Prins, G. S., Geng, H."Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome". Biomedical Reports 24.2 (2026): 27.
Chicago
Ham, H., Senthil, P., Tan, S. C., Sargis, R. M., Prins, G. S., Geng, H."Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome". Biomedical Reports 24, no. 2 (2026): 27. https://doi.org/10.3892/br.2025.2100
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