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Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors

  • Authors:
    • Yingzi Deng
    • Yifei Li
    • Ruobing Li
    • Xiaohui Guo
    • Yan Liu
    • Shuqing Wang
    • Juan Zhang
    • Mi Li
    • Lina Zhao
    • Haifeng Cai
    • Yunfeng Zhang
    • Fen Hu
  • View Affiliations / Copyright

    Affiliations: Department of Bioinformatics, College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China, Department of Bioinformatics, College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China, The Second Department of Breast Surgery, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, The Second Department of Breast Surgery, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Tangshan Key Laboratory of Agricultural Pathogenic Fungi and Toxins, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 260
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    Published online on: July 21, 2025
       https://doi.org/10.3892/mmr.2025.13625
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Abstract

WD repeat and SOCS box containing 2 (WSB2) is an E3 ubiquitin ligase that might be involved in regulating protein stability, thus performing important roles in the development of different types of cancer. However, the biological significance of WSB2 in pan‑cancer is unclear. Pan‑cancer analysis with the online platforms UALCAN and TIMER2.0. revealed that the expression levels of WSB2 were increased in various types of tumors, including breast invasive carcinoma, uterine corpus endometrial carcinoma, liver hepatocellular carcinoma and were decreased in other types such as colon adenocarcinoma, kidney chromophobe and rectum adenocarcinoma, compared with that in their corresponding normal tissues. In addition, pan‑cancer analysis using The Human Protein Atlas database indicated that WSB2 expression levels vary across different cancer types. Reverse transcription‑quantitative PCR (RT‑qPCR) revealed that WSB2 expression varied in 11 different cell lines. Promoter activity analysis indicates that specificity protein 1 carries out a key role in regulating WSB2 expression by binding to its promoter region. UALCAN and Kaplan‑Meier analysis were used to assess the pathological stage and prognostic value of WSB2 in pan‑cancer. Finally, overexpression of WSB2 promoted the proliferation and migration of MCF‑7 and MDA‑MB‑231 cells. Western blotting revealed that WSB2 increased the levels of vimentin, Snail and ERK1/2, and inhibited the expression of p53 and E‑cadherin in MDA‑MB‑231 and MCF‑7 cells. Transcriptome sequencing analysis identified 118 differentially expressed genes associated with WSB2 overexpression, which were mainly enriched in the ‘p53 signaling pathway’. Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.
View Figures

Figure 1

Expression of WSB2 in cell lines and
tissues. (A) P-value heat maps of the TIMER and UALCAN analyses;
red indicates that the expression of WSB2 in cancer tissues is
increased compared with that in normal tissues, while blue
indicates that the expression of WSB2 in cancer tissues is
decreased *P<0.05, **P<0.01, ***P<0.001 vs. normal. (B)
Immunohistochemistry images of WSB2 protein expression from the
Human Protein Atlas database. (C) Expression of WSB2 in 11 cell
lines, as detected using RT-qPCR, *P<0.05 vs. SVCT cells,
#P<0.05 vs. MCF-10A cells. WSB2, WD repeat and SOCS
box containing 2; BRCA, breast invasive carcinoma; LIHC, liver
hepatocellular carcinoma; PRAD, prostate adenocarcinoma; UCEC,
uterine corpus endometrial carcinoma; COAD, colon adenocarcinoma;
THCA, thyroid carcinoma; PRCC, papillary renal cell carcinoma;
CHOL, cholangiocarcinoma; LUSC, Lung squamous cell carcinoma;
HNSC-HPV+, Human papillomavirus-Positive Head and Neck Squamous
Cell Carcinoma; CESC, Cervical and endocervical cancers; KIRP,
Kidney renal papillary cell carcinoma; STAD, Stomach
adenocarcinoma; BLCA, Bladder Urothelial Carcinoma; ESCA,
Esophageal carcinoma; PCPG, Pheochromocytoma and Paraganglioma;
SKCM, Skin Cutaneous Melanoma; PAAD, Pancreatic Adenocarcinoma;
LUAD, Lung adenocarcinoma; KIRC, Kidney renal clear cell carcinoma;
GBM, Glioblastoma multiforme; KICH, Kidney Chromophobe; READ,
Rectum adenocarcinoma.

Figure 2

Binding relationship between the WSB2
promoter and SP1. (A) Schematic diagram of the structure of three
WSB2 promoter luciferase expression vectors,
pWSB2-1.6k/pWSB2-0.8k/pWSB2-0.3k. (B) Relative levels of luciferase
activity of pWSB2-1.6k/pWSB2-0.8k/pWSB2-0.3k. (C) Relative levels
of luciferase activity of pWSB2-1.6k after treatment with
plicamycin. (D) The binding site of SP1 in the endogenous WSB2
promoter, as analyzed using chromatin immunoprecipitation-qPCR in
MDA-MB-231 cells, *P<0.05. (E) Reverse transcription-qPCR
analysis of the mRNA expression levels of SP1 and WSB2 in
MDA-MB-231, MCF-7, A2780, U87 MG and HeLa cells after
pCMV-SP1(human)-3×FLAG-Neo overexpression. (F) TIMER and UALCAN
data prediction of the correlation between SP1 and WSB2 expression
in a variety of types of cancer. Blue box, R>0.3. *P<0.05,
**P<0.01. WSB2, WD repeat and SOCS box containing 2; q,
quantitative; SP1, specificity protein-1.

Figure 3

Relationship between WD repeat and
SOCS box containing 2 gene expression and cancer survival and
prognosis. The Kaplan-Meier online database was used to analyze the
relationship between WSB2 expression and (A) overall survival and
(B) disease-free survival in The Cancer Genome Atlas and Gene
Expression Omnibus datasets. BRCA, breast invasive carcinoma; LIHC,
liver hepatocellular carcinoma; CESC, cervical squamous cell
carcinoma; HNSC, head and neck squamous cell carcinomas; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; PPGLs,
pheochromocytomas and paragangliomas; TGCT, testicular germ cell
tumors; THCA, thyroid carcinoma; SARC, sarcoma; HR, hazard
ratio.

Figure 4

WSB2 promotes the proliferation and
migration of breast cancer cells. (A) Reverse
transcription-quantitative PCR and (B) western blotting were used
to detect the effect of WSB2 overexpression in MDA-MB-231 and MCF-7
cells. (C) Viability of MDA-MB-231 and MCF-7 cells was evaluated
using a CCK-8 assay. (D) Representative images and (E) the
quantification of the number of MDA-MB-231 and MCF-7 cells in the S
phase evaluated using an 5 ethynyl-2′-deoxyuridine assay. (F)
Representative images of colony formation ability of MDA-MB-231 and
MCF-7cells. (G) Representative images and (H) quantification of
wound healing and (I) colony formation ability of MDA-MB-231 and
MCF-7cells. (J) Transwell assays to determine the migration ability
of MDA-MB-231and MCF-7cells. (K) ERK1/2, p53 and PCNA and (L)
Snail, E-cadherin and Vimentin protein levels in MDA-MB-231 and
MCF-7 cells were detected using western blotting. *P<0.05,
**P<0.01, ***P<0.001. WSB2, WD repeat and SOCS box containing
2.

Figure 5

Detection of DEGs regulated by WSB2.
(A) MDA-MB-231 cells were transfected with pCMV-HA or pCMV-HA-WSB2.
Volcano map of DEGs, which was obtained from the transcriptome
sequencing analysis results. Red dots indicate significantly
upregulated genes and green dots indicate significantly
downregulated genes. (B) Top 10 Kyoto Encyclopedia of Genes and
Genomes pathway items enriched for DEGs. (C) NUPR1, MDM2 and
LDLRAD4 mRNA levels were detected in MDA-MB-231, MCF-7, A2780, U87
MG and HeLa cells using reverse transcription-quantitative PCR.
Compared with HA-vector, *P<0.05, **P<0.01, ***P<0.001 vs.
HA-vector. n.s, no significance; WSB2, WD repeat and SOCS box
containing 2; DEGs, differentially expressed genes; OE,
overexpressed; NC, negative control; LDLRAD4, low density
lipoprotein receptor class A domain containing 4; MDM2, mouse
double min 2; NUPR1, nuclear protein 1.
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Copy and paste a formatted citation
Spandidos Publications style
Deng Y, Li Y, Li R, Guo X, Liu Y, Wang S, Zhang J, Li M, Zhao L, Cai H, Cai H, et al: Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors. Mol Med Rep 32: 260, 2025.
APA
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S. ... Hu, F. (2025). Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors. Molecular Medicine Reports, 32, 260. https://doi.org/10.3892/mmr.2025.13625
MLA
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S., Zhang, J., Li, M., Zhao, L., Cai, H., Zhang, Y., Hu, F."Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors". Molecular Medicine Reports 32.4 (2025): 260.
Chicago
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S., Zhang, J., Li, M., Zhao, L., Cai, H., Zhang, Y., Hu, F."Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors". Molecular Medicine Reports 32, no. 4 (2025): 260. https://doi.org/10.3892/mmr.2025.13625
Copy and paste a formatted citation
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Spandidos Publications style
Deng Y, Li Y, Li R, Guo X, Liu Y, Wang S, Zhang J, Li M, Zhao L, Cai H, Cai H, et al: Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors. Mol Med Rep 32: 260, 2025.
APA
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S. ... Hu, F. (2025). Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors. Molecular Medicine Reports, 32, 260. https://doi.org/10.3892/mmr.2025.13625
MLA
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S., Zhang, J., Li, M., Zhao, L., Cai, H., Zhang, Y., Hu, F."Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors". Molecular Medicine Reports 32.4 (2025): 260.
Chicago
Deng, Y., Li, Y., Li, R., Guo, X., Liu, Y., Wang, S., Zhang, J., Li, M., Zhao, L., Cai, H., Zhang, Y., Hu, F."Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors". Molecular Medicine Reports 32, no. 4 (2025): 260. https://doi.org/10.3892/mmr.2025.13625
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