ArticleWorld journal of gastroenterology2017
Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma.
Article in World journal of gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Epithelial to Mesenchymal Transition Transcriptional Regulator ZEB1 in Liver Cancer: Oncogenic Roles and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression.Frontiers in oncology · 2022Article
- Identification of an epithelial-mesenchymal transition-related lncRNA prognostic signature for patients with glioblastoma.Scientific reports · 2021Article
- Targeting Cullin-RING E3 Ubiquitin Ligase 4 by Small Molecule Modulators.Journal of cellular signaling · 2021Article
- CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6.Molecular medicine reports · 2021Article
- Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma.International journal of clinical oncology · 2020Article
- CUL4A expression is associated with tumor stage and prognosis in nasopharyngeal carcinoma.Medicine · 2019Observational
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo explore the functional role of cullin 4A (CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma (PHCC).
methodsThe expression of CUL4A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry (IHC) was adopted to investigate the relationship between CUL4A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival (OS) and progression-free survival (PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition (EMT) markers was verified in cells with CUL4A knockdown or overexpression. The relationship between CUL4A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays.
resultsCUL4A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4A expression; as well as three related to PFS: N stage, TNM stage and high CUL4A expression. Further multivariate logistic regression analysis identified high CUL4A expression as the only independent prognostic factor for PHCC. Moreover, CUL4A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4A in promoting the EMT and metastasis.
conclusionCUL4A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4A may be a potential therapeutic target for PHCC.
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