ECRG4 Represses Cell Proliferation and Invasiveness via NFIC/OGN/NF-κB Signaling Pathway in Bladder Cancer
Xin Liang1,2, Jiangang Gao2, Quan Wang3
1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Abstract:
Bladder cancer (BCa) is a malignant tumor in the urinary system with high cancer-related mortality worldwide. However, the molecular mechanisms of many genes dysregulated in BCa are still unclear. Herein, we showed that esophageal cancer-related gene-4 (ECRG4), which is downregulated in BCa tissues and cell lines, has a positive correlation with osteoglycin (OGN). Further functional experimental studies suggested that both ECRG4 and OGN inhibit cell proliferation, migration, and invasion in BCa cells. Moreover, ECRG4 acts as a tumor repressor and promotes the expression of OGN via the upregulation of nuclear factor 1 C-type (NFIC), which can bind to the promoter region of OGN and regulate its transcription. Bioinformatics analysis revealed that NFIC is downregulated in BCa tissues and has a positive correlation with ECRG4 or OGN. Esophageal cancer-related gene-4 could positively regulate the protein levels of NFIC in BCa cells. In addition, we demonstrated for the first time that ECRG4 inhibits the nuclear factor (NF)-κB signaling pathway via the upregulation of OGN in BCa cells. Overall, these findings provide evidence that both ECRG4 and OGN function as tumor repressors and that overexpression of ECRG4 inhibits the NF-κB signaling pathway by promoting NFIC/OGN signaling in BCa cells. Our results reveal the molecular regulatory mechanisms of the ECRG4-mediated repression of the NFIC/OGN/NF-κB signaling pathway in BCa and provide potential biomarkers or therapeutic targets for BCa.
Insights
Esophageal cancer-related gene-4 (ECRG4) and osteoglycin (OGN) suppress bladder cancer (BCa) progression. ECRG4 promotes OGN expression via NFIC, inhibiting the NF-κB pathway, offering potential BCa biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Bladder cancer (BCa) presents high mortality, with unclear molecular mechanisms for many dysregulated genes.
- Esophageal cancer-related gene-4 (ECRG4) is downregulated in BCa, suggesting a potential tumor-suppressive role.
Purpose of the Study:
- To elucidate the molecular mechanisms of ECRG4 in bladder cancer.
- To investigate the relationship between ECRG4, osteoglycin (OGN), and nuclear factor 1 C-type (NFIC) in BCa.
Main Methods:
- Gene expression analysis in BCa tissues and cell lines.
- Functional assays assessing cell proliferation, migration, and invasion.
- Bioinformatics analysis of gene correlations and promoter binding.
- Investigation of signaling pathway modulation (NF-κB).
Main Results:
- ECRG4 and OGN are downregulated in BCa and inhibit tumor progression.
- ECRG4 upregulates NFIC, which in turn promotes OGN transcription.
- ECRG4 positively regulates NFIC protein levels.
- ECRG4 inhibits the NF-κB signaling pathway through OGN upregulation.
Conclusions:
- ECRG4 and OGN act as tumor suppressors in bladder cancer.
- The ECRG4-NFIC-OGN axis inhibits BCa progression by repressing the NF-κB pathway.
- This pathway presents potential therapeutic targets and biomarkers for BCa.
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