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Fibronectin 1 as a Key Gene in the Genesis and Progression of Cadmium-Related Bladder Cancer

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Abstract

Exposure to cadmium (Cd), a non-essential heavy metal, leads to the malignant transformation of urothelial cells and promotes bladder cancer (BC) development, but the mechanisms are unclear. Therefore, we aimed to explore the possible molecules associated with Cd-related BC. By analyzing and mining biological big data in public databases, we screened genes associated with the malignant transformation of uroepithelial cells caused by Cd and further screened the key gene associated with BC prognosis from these genes. The possible roles of the key gene in BC progression were then further explored through biological big data analysis and cellular experiments. Data mining yielded a total of 387 malignant transformation-related genes, which were enriched in multiple cancer-related signaling pathways, such as cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, and Jak-STAT signaling pathway. Further screening identified Fibronectin 1 (FN1) as the key gene. High expression of FN1 was associated with the advanced pathologic stage, T stage, N stage, and M stage and predicted an unfavorable outcome in BC patients. FN1 expression was positively associated with the infiltration of several types of immune cells, particularly tumor-associated macrophages and cancer-associated fibroblasts. Overexpression of FN1 could be detected in Cd-treated urothelial cells and BC cell lines. Interestingly, silencing of FN1 impaired the proliferation and invasive capacity of BC cells. In conclusion, the present study provides new insight into the mechanism of Cd-related BC. FN1 might be a prognostic marker and therapeutic target for BC. Future studies are needed to confirm these results.

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Abbreviations

Cd :

Cadmium

BC :

Bladder cancer

DEGs :

Differentially expressed genes

GEO :

Gene Expression Omnibus

GO :

Gene Ontology

KEGG :

Kyoto Encyclopedia of Genes and Genomes

PPI :

Protein–protein interaction

TCGA :

The Cancer Genome Atlas

DMEM :

Dulbecco’s modified Eagle’s medium

FN1 :

Fibronectin 1

FDR :

False discovery rate

CAFs :

Cancer-associated fibroblasts

TME :

Tumor microenvironment

TAMs :

Tumor-associated macrophages

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Authors and Affiliations

  1. College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

    Liang Zhang, Minghan Song & Yi Zhu

  2. Affiliated Hospital of Guizhou Medical University, Guiyang, China

    Liang Zhang & Aoshuang Chang

  3. Xinqiao Hospital, Army Medical University, Chongqing, China

    Yan Wang & Wenlei Zhuo

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  1. Liang Zhang
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  2. Yan Wang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by LZ, YW, MS, and AC. The first draft of the manuscript was written by LZ, WZ, and YZ. All authors read, reviewed, and approved the final manuscript.

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Correspondence to Yi Zhu.

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Zhang, L., Wang, Y., Song, M. et al. Fibronectin 1 as a Key Gene in the Genesis and Progression of Cadmium-Related Bladder Cancer. Biol Trace Elem Res 201, 4349–4359 (2023). https://doi.org/10.1007/s12011-022-03510-1

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