ArticleBMC medical genomics2020
TOP2A and CENPF are synergistic master regulators activated in cervical cancer.
Article in BMC medical genomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Transcription factor activity profiling uncovers prognostic subtypes and a novel oncogenic role for PRDM4 in NSMP endometrial carcinoma.BMC cancer · 2026Article
- Topoisomerase inhibitors in cervical cancer: mechanistic insights and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2026Review
- Recent advancement in inflammatory biomarkers for cervical cancer diagnosis and therapy.Frontiers in oncology · 2026Review
- The expression and clinical significance of SIRT5, H2A and TOP2A in cervical cancer.Frontiers in oncology · 2026Article
- Single cell-RNA sequencing reveal TOP2A as a key driver of hepatocellular carcinoma progression.Scientific reports · 2025Article
- CENPF overexpression in bladder cancer cells enhances proliferation, migration, invasion, and apoptosis.Scientific reports · 2025Article
- Multiple cell types guided by neurocytes orchestrate horn bud initiation in dairy goats.Genetics, selection, evolution : GSE · 2025Article
- Reduction of NFX1-123 and HPV 16 E6 and E7 Decreased Telomerase and CENP-F in Cervical Cancer Cell Lines.Cancers · 2025Article
- Advances in research on malignant tumors and targeted agents for TOP2A (Review).Molecular medicine reports · 2025Review
- TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.Cancer biology & therapy · 2024Article
- A Four-Gene Panel for the Prediction of Prognosis and Immune Cell Enrichment in Gliomas.Molecular biotechnology · 2024Article
- Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.International journal of molecular sciences · 2024Article
- Cell-Cycle-related Protein Centromere Protein F Deficiency Inhibits Cervical Cancer Cell Growth by Inducing Ferroptosis Via Nrf2 Inactivation.Cell biochemistry and biophysics · 2024Article
- Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.Cells · 2024Article
- Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.Frontiers in genetics · 2024Article
- Intraglandular dissemination: a special pathological feature.Frontiers in oncology · 2024Review
- Long Non-Coding RNA Small Nucleolar RNA Host Gene 4 Induced by Transcription Factor SP1 Promoted the Progression of Nasopharyngeal Carcinoma Through Modulating microRNA-510-5p/Centromere Protein F Axis.Biochemical genetics · 2023Article
- Single-cell sequencing analysis reveals development and differentiation trajectory of Schwann cells manipulated by M. leprae.PLoS neglected tropical diseases · 2023Article
- TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?Endocrine pathology · 2023Article
- LINC00536 knockdown inhibits breast cancer cells proliferation, invasion, and migration through regulation of the miR-4282/centromere protein F axis.The Kaohsiung journal of medical sciences · 2022Article
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIdentification of master regulators (MRs) using transcriptome data in cervical cancer (CC) could help us to develop biomarkers and find novel drug targets to fight this disease.
methodsWe performed differential expression (DE) analyses of public microarray and RNA-seq transcriptome data of CC and normal cervical tissues (N). Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER) was used to convert the DE outcomes to differential activity (DA) signature for MRs. Synergy analysis was conducted to study synergistic effect of MR-pairs. TCGA and microarray data were used to test the association of expression of a MR and a clinical feature or a molecular feature (e.g. somatic mutations). Various bioinformatic tools/websites (DAVID, GEPIA2, Oncomine, cBioPortal) were used to analyze the expression of the top MRs and their regulons.
resultsTen DE and 10 DA signatures were generated for CC. Two MRs, DNA topoisomerase II alpha (TOP2A) and centromere protein F (CENPF) were found to be up-regulated, activated and synergistic in CC compared to N across the 10 datasets. The two MRs activate a common set of genes (regulons) with functions in cell cycle, chromosome, DNA damage etc. Higher expression of CENPF was associated with metastasis. High expression of both MRs is associated with somatic mutation of a set of genes including tumor suppressors (TP53, MSH2, RB1) and genes involved in cancer pathways, cell cycle, DNA damage and repair. The magnitude of up-regulation and the absolute expression level of both MRs in CC are significantly higher compared to many other cancer types.
conclusionTOP2A and CENPF are a synergistic pair of MRs that are overexpressed and activated in CC. Their high expression is correlated with some prognosis features (e.g. metastasis) and molecular features (e.g. somatic mutations) and distinctly high in CC vs. many other cancer types. They may be good biomarkers and anticancer drug targets for CC.
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