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Article Open Access

KRT14 activated by transcription factor E2F1 promotes bladder cancer progression

  • Authors:
    • Xingheng Chen
    • Sinan Liu
    • Xiaosong Zhang
    • Xiang Chen
    • Chenlu Wang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Clinical Innovation Research Center of Nantong University and Nantong City No. 1 People's Hospital, Nantong, Jiangsu 226001, P.R. China, Department of Urology, Nantong Tongzhou District People's Hospital, Nantong, Jiangsu 226300, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 529
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    Published online on: September 24, 2026
       https://doi.org/10.3892/ol.2026.15884
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Abstract

Bladder cancer is one of the most common cancers in the world, and its high malignancy threatens human health. Therefore, it is vital to explore new therapeutic targets for the early diagnosis and prognosis evaluation of bladder cancer. Keratin 14 (KRT14) is the oncogene of numerous cancers, but its role and mechanism in bladder cancer are not completely clear. The present study aimed to assess the molecular mechanism of KRT14 in bladder cancer. Bioinformatics analyses were performed to screen KRT14 as an oncogene in bladder cancer. Moreover, KRT14 small interfering RNA and KRT14 overexpression plasmids were transfected into 5637 and RT4 bladder cancer cells. Subsequently, Transwell, Cell Counting Kit‑8 and cell colony formation assays were performed to assess changes in cell phenotype. Finally, bioinformatics analysis was performed to screen for transcription factors of KRT14. The results demonstrated that KRT14 was highly expressed in bladder cancer tissues and cell lines, and its expression was associated with a poor prognosis. KRT14 knockdown suppressed proliferation, migration and invasion of 5637 and RT4 cells, whereas ectopic KRT14 overexpression demonstrated the inverse phenotypic changes. E2F transcription factor 1 (E2F1) is an upstream transcription factor of KRT14 and the effects of KRT14 silencing on 5637 cell migration and invasion were attenuated by E2F1 overexpression. In addition, Gene Set Cancer Analysis, drug sensitivity correlation analysis and molecular docking simulation predicted that afatinib, erlotinib and vandetanib may serve as candidate small molecules with potential binding affinity to KRT14. This provides preliminary clues for developing KRT14‑intervening agents for bladder cancer. In conclusion, KRT14 is an oncogenic gene that promotes bladder cancer progression upon transcriptional activation by the upstream transcription factor E2F1. Its high expression is associated with poor prognosis, supporting its potential as a prognostic biomarker and therapeutic target in bladder cancer.
View Figures

Figure 1

Analysis of GEO dataset GSE77883. (A)
Principal component analysis of dataset GSE77883. (B) Volcano plot
of differentially expressed genes. The red dots represent
significantly upregulated genes, while the blue dots represent
significantly downregulated genes. (C) Heat map of partially
differentially expressed genes, with blue representing the control
group and red representing the experimental group. (D) Box plot of
gene expression in 6 samples of the GSE77883 dataset. GEO, Gene
Expression Omnibus; PC, principal component; ref, reference.

Figure 2

Identification of the oncogene KRT14
in bladder cancer. (A) Protein-protein interaction network
screening vital differentially expressed genes in bladder cancer.
(B) Expression of KRT14 in bladder cancer in paired samples. (C)
Expression of RNA-sequencing data of KRT14 in bladder cancer. (D)
OS of KRT14 in bladder cancer (P=0.013). (E) RFS of KRT14 in
bladder cancer (P=0.043). (F) ROC curve of TCGA-BLCA according to
the expression of KRT14 (P<0.001). **P<0.01; ***P<0.001.
KRT14, keratin 14; OS, overall survival; RFS, regression-free
survival; ROC, receiver operating characteristic; TCGA-BLCA, The
Cancer Genome Atlas-Bladder Cancer; TPM, transcripts per million;
HR, hazard ratio; CI, confidence interval; AUC, area under the
curve; TPR, true positive rate; FPR, false positive rate.

Figure 3

Analysis of the expression patterns
of KRT14 in single-cell sequencing and the Human Protein Atlas
datasets. (A) UMAP visualization of integrated bladder cancer
single-cell datasets. A total of 10 cell subtypes were annotated by
canonical lineage markers. (B) The specific expression of KRT14 in
various cell types. (C) Analysis of differential expression of
KRT14 proteins in bladder cancer tissues and normal bladder tissues
(scale bar, 100 µm). Images are available from https://www.proteinatlas.org/ENSG00000186847-KRT14/tissue/urinary+bladder.
KRT14, keratin 14; UMAP, Uniform Manifold Approximation and
Projection.

Figure 4

High expression of KRT14 in bladder
cancer tissues and cells. (A) Protein expression levels of KRT14 in
bladder cancer tissues. (B) mRNA expression levels of KRT14 in
bladder cancer tissues. (C) Protein expression levels of KRT14 in
bladder cancer cell lines. (D) mRNA expression level of KRT14 in
bladder cancer cell lines. SV-HUC-1 served as the normal control
cell line. **P<0.01; ***P<0.001. KRT14, keratin 14.

Figure 5

Silencing of KRT14 inhibits the
proliferation of bladder cancer cells. Silencing efficiency of
KRT14-interfering lentivirus in (A) 5637 and (B) RT4 cells. (C)
Transwell assays were used to assess the migration of 5637 and RT4
cells. Colony forming assays were performed in (D) 5637 and (E) RT4
cells. Cell Counting Kit-8 assay in (F) 5637 and (G) RT4 cells.
*P<0.05; **P<0.01. KRT14, keratin 14; si, small interfering
RNA; NC, negative control.

Figure 6

Overexpression of KRT14 promotes the
progression of bladder cancer. Overexpression efficiency of KRT14
in (A) 5637 cells and (B) RT4 cells. (C) Transwell assays were used
to assess the migration of 5637 and RT4 cells. Colony forming assay
was performed in (D) 5637 and (E) RT4 cells. Cell Counting Kit-8
assays were performed in (F) 5637 and (G) RT4 cells. *P<0.05.
KRT14, keratin 14; OE, overexpression; NC, negative control.

Figure 7

KRT14 is directly regulated by
transcription factor E2F1. (A) MOTIF was used to predict the
binding site of KRT14 promoter and E2F1. (B) Co-expression scatter
plot of E2F1 and KRT14 mRNA expression in TCGA-BLCA patient
samples. (C) Schematic diagram of the binding effects of KRT14
promoter and E2F1. (D) Luciferase assay for assessing binding
effects. (E) 5637 and (F) RT4 cells were transfected with an E2F1
overexpression vector or empty pENTER vector. The mRNA levels of
KRT14 were assessed using reverse transcription-quantitative PCR.
(G) Protein levels of KRT14 were assessed using western blotting.
Chromatin immunoprecipitation-PCR was performed in (H) 5637 and (I)
RT4 cells using specific antibodies against E2F1. (J) Cell
viability was assessed using Cell Counting Kit-8 assays in 5637
cells transfected with KRT14 siRNA or E2F1 overexpression vector.
(K) Cell migration and invasion were measured using CCK-8 assays.
*P<0.05; **P<0.01; ***P<0.001. KRT14, keratin 14; E2F1,
E2F transcription factor 1; TCGA-BLCA, The Cancer Genome
Atlas-Bladder Cancer; si, small interfering RNA; NC, negative
control; TPM, transcripts per million; mut, mutant; ns, not
significant.

Figure 8

Drug sensitivity analysis and
molecular docking. (A) Gene Set Cancer Analysis correlation
analysis was used to screen candidate small molecules with
predicted potential binding to KRT14. (B) Structure of afatinib and
its molecular docking with KRT14. (C) Structure of erlotinib and
its molecular docking with KRT14. (D) Structure of vandetanib and
its molecular docking with KRT14. KRT14, keratin 14; FDR, false
discovery rate.
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Copy and paste a formatted citation
Spandidos Publications style
Chen X, Liu S, Zhang X, Chen X and Wang C: KRT14 activated by transcription factor E2F1 promotes bladder cancer progression. Oncol Lett 32: 529, 2026.
APA
Chen, X., Liu, S., Zhang, X., Chen, X., & Wang, C. (2026). KRT14 activated by transcription factor E2F1 promotes bladder cancer progression. Oncology Letters, 32, 529. https://doi.org/10.3892/ol.2026.15884
MLA
Chen, X., Liu, S., Zhang, X., Chen, X., Wang, C."KRT14 activated by transcription factor E2F1 promotes bladder cancer progression". Oncology Letters 32.5 (2026): 529.
Chicago
Chen, X., Liu, S., Zhang, X., Chen, X., Wang, C."KRT14 activated by transcription factor E2F1 promotes bladder cancer progression". Oncology Letters 32, no. 5 (2026): 529. https://doi.org/10.3892/ol.2026.15884
Copy and paste a formatted citation
x
Spandidos Publications style
Chen X, Liu S, Zhang X, Chen X and Wang C: KRT14 activated by transcription factor E2F1 promotes bladder cancer progression. Oncol Lett 32: 529, 2026.
APA
Chen, X., Liu, S., Zhang, X., Chen, X., & Wang, C. (2026). KRT14 activated by transcription factor E2F1 promotes bladder cancer progression. Oncology Letters, 32, 529. https://doi.org/10.3892/ol.2026.15884
MLA
Chen, X., Liu, S., Zhang, X., Chen, X., Wang, C."KRT14 activated by transcription factor E2F1 promotes bladder cancer progression". Oncology Letters 32.5 (2026): 529.
Chicago
Chen, X., Liu, S., Zhang, X., Chen, X., Wang, C."KRT14 activated by transcription factor E2F1 promotes bladder cancer progression". Oncology Letters 32, no. 5 (2026): 529. https://doi.org/10.3892/ol.2026.15884
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