ArticlePloS one2014
Promoter hypermethylation of KLF4 inactivates its tumor suppressor function in cervical carcinogenesis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 61 citations in OpenAlex.
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- 4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2023Article
- Low RNA stability signifies strong expression regulatability of tumor suppressors.Nucleic acids research · 2023Article
- Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.Current issues in molecular biology · 2023Article
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- In utero and postnatal exposure to Foeniculum vulgare and Linum usitatissimum seed extracts: modifications of key enzymes involved in epigenetic regulation and estrogen receptors expression in the offspring's ovaries of NMRI mice.BMC complementary medicine and therapies · 2023Article
- Higher Expression of DNA (de)methylation-Related Genes Reduces Adipogenicity in Dental Pulp Stem Cells.Frontiers in cell and developmental biology · 2022Article
- Identification of Key Pathways and Establishment of a Seven-Gene Prognostic Signature in Cervical Cancer.Journal of oncology · 2022Article
- CRISPR-mediated promoter de/methylation technologies for gene regulation.Archives of pharmacal research · 2020Review
- Inducible transgene expression in PDX models in vivo identifies KLF4 as a therapeutic target for B-ALL.Biomarker research · 2020Article
- Role of DNA Methylation in the Resistance to Therapy in Solid Tumors.Frontiers in oncology · 2020Review
- SALL4 promotes the tumorigenicity of cervical cancer cells through activation of the Wnt/β-catenin pathway via CTNNB1.Cancer science · 2019Article
- Chronic Exposure of Mice to Bisphenol-A Alters Uterine Fibroblast Growth Factor Signaling and Leads to Aberrant Epithelial Proliferation.Endocrinology · 2019Article
- Polo-Like Kinase 1 phosphorylates and stabilizes KLF4 to promote tumorigenesis in nasopharyngeal carcinoma.Theranostics · 2019Article
- Dietary Compounds as Epigenetic Modulating Agents in Cancer.Frontiers in genetics · 2019Review
- Novel tumor-suppressor function of KLF4 in pediatric T-cell acute lymphoblastic leukemia.Experimental hematology · 2017Review
- Establishment of anBioscience reports · 2017Article
- Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway.Leukemia · 2017Article
- Review
- A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome.International journal of women's health · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe KLF4 gene has been shown to be inactivated in cervical carcinogenesis as a tumor suppressor. However, the mechanism of KLF4 silencing in cervical carcinomas has not yet been identified. DNA methylation plays a key role in stable suppression of gene expression.
methodsThe methylation status of the KLF4 promoter CpG islands was analyzed by bisulfite sequencing (BSQ) in tissues of normal cervix and cervical cancer. KLF4 gene expression was detected by RT-PCR, immunohistochemistry and western blot. KLF4 promoter methylation in cervical cancer cell line was determined by BSQ and methylation-specific polymerase chain reaction (MS-PCR). Cell proliferation ability was detected by cell growth curve and MTT assay.
resultsThe methylated allele was found in 41.90% of 24 cervical cancer tissues but only in 11.11% of 11 normal cervix tissues (P<0.005). KLF4 mRNA levels were significantly reduced in cervical cancer tissues compared with normal cervix tissues (P<0.01) and KLF4 mRNA expression showed a significant negative correlation with the promoter hypermethylation (r = -0.486, P = 0.003). Cervical cancer cell lines also showed a significant negative correlation between KLF4 expression and hypermethylation. After treatment with the demethylating agent 5-Azacytidine (5-Aza), the expression of KLF4 in the cervical cancer cell lines at both mRNA and protein levels was drastically increased, the cell proliferation ability was inhibited and the chemosensitivity for cisplatin was significantly increased.
conclusionKLF4 gene is inactivated by methylation-induced silencing mechanisms in a large subset of cervical carcinomas and KLF4 promoter hypermethylation inactivates the gene's function as a tumor suppressor in cervical carcinogenesis.
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