ArticleOncotarget2016
Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- Selagibenzophenone B and Its Derivatives:ACS bio & med chem Au · 2024Article
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Reduced PDE4D7 in prostate cancer correlates with genomic downregulation within the upstream PDE4D coding region.Future science OA · 2023Article
- The CAPRA&PDE4D5/7/9 Prognostic Model Is Significantly Associated with Adverse Post-Surgical Pathology Outcomes.Cancers · 2022Article
- Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers.Genome medicine · 2022Article
- An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.Clinical and translational medicine · 2021Article
- Phosphodiesterase 4D Depletion/Inhibition Exerts Anti-Oncogenic Properties in Hepatocellular Carcinoma.Cancers · 2021Article
- PDE4 subtypes in cancer.Oncogene · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD-1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway.Oncology letters · 2019Article
- The Association of the Long Prostate Cancer Expressed PDE4D Transcripts to Poor Patient Outcome Depends on the Tumour's TMPRSS2-ERG Fusion Status.Prostate cancer · 2019Article
- Gastric cancer may share genetic predisposition with esophageal squamous cell carcinoma in Chinese populations.Journal of human genetics · 2018Article
- Gene-expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma.Oncology letters · 2018Article
- Identifying a panel of genes/proteins/miRNAs modulated by arsenicals in bladder, prostate, kidney cancers.Scientific reports · 2018Article
- miR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D.American journal of cancer research · 2018Article
- The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.Prostate cancer · 2018Article
- Investigation of the molecular mechanisms underlying postoperative recurrence in prostate cancer by gene expression profiling.Experimental and therapeutic medicine · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase 4D7 was recently shown to be specifically over-expressed in localized prostate cancer, raising the question as to which regulatory mechanisms are involved and whether other isoforms of this gene family (PDE4D) are affected under the same conditions.We investigated PDE4D isoform composition in prostatic tissues using a total of seven independent expression datasets and also included data on DNA methylation, copy number and AR and ERG binding in PDE4D promoters to gain insight into their effect on PDE4D transcription.We show that expression of PDE4D isoforms is consistently altered in primary human prostate cancer compared to benign tissue, with PDE4D7 being up-regulated while PDE4D5 and PDE4D9 are down-regulated. Disease progression is marked by an overall down-regulation of long PDE4D isoforms, while short isoforms (PDE4D1/2) appear to be relatively unaffected. While these alterations seem to be independent of copy number alterations in the PDE4D locus and driven by AR and ERG binding, we also observed increased DNA methylation in the promoter region of PDE4D5, indicating a long lasting alteration of the isoform composition in prostate cancer tissues.We propose two independent metrics that may serve as diagnostic and prognostic markers for prostate disease: (PDE4D7 - PDE4D5) provides an effective means for distinguishing PCa from normal adjacent prostate, whereas PDE4D1/2 - (PDE4D5 + PDE4D7 + PDE4D9) offers strong prognostic potential to detect aggressive forms of PCa and is associated with metastasis free survival. Overall, our findings highlight the relevance of PDE4D as prostate cancer biomarker and potential drug target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.