ArticleOncotarget2017
Opposing roles of PIK3CA gene alterations to EZH2 signaling in non-muscle invasive bladder cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Pooled it
- Predictive Molecular Biomarkers of Bladder Cancer Identified by Next-Generation Sequencing-Preliminary Data.Journal of clinical medicine · 2024Article
- Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer.Cancers · 2021Review
- Article
- Advances in urinary biomarker discovery in urological research.Investigative and clinical urology · 2020Review
- Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status.Scientific reports · 2019Article
- Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression.Nature medicine · 2019Article
- Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet.Frontiers in genetics · 2019Review
- Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta-analysis.American journal of translational research · 2018Review
- MiR-101 inhibits ovarian carcinogenesis by repressing the expression of brain-derived neurotrophic factor.FEBS open bio · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high rates of tumor recurrence and progression represent a major clinical problem in non-muscle invasive bladder cancer. Previous data showed that EZH2-dependent signaling mediates these processes, whereas the frequent alterations of PIK3CA gene (copy gains and mutations) are predictive of reduced recurrence. Here we show, using clinical samples and bladder cancer cell lines, a functional interaction between EZH2- and PIK3CA-dependent signaling pathways. PIK3CA alterations mediated, on the one hand, the increased expression of two miRNAs, miR-101 and miR-138, which posttranscriptionally downregulate EZH2 expression. On the other hand, PIK3CA alterations facilitate the activation of Akt which phosphorylates EZH2 on Ser21, precluding the trimethylation of histone H3 in K27. Remarkably the increased expression of miR101 or miR138 and the expression of Ser21-phosphorylated EZH2 are good prognostic factors regarding non-muscle invasive bladder cancer recurrence and progression. Collectively, this study provides molecular evidences indicating that the gene expression rewiring occurring in primary bladder tumors, associated with increased EZH2 expression and activity and mediating the increased recurrence and progression risk, are prevented by PIK3CA-dependent signaling. This molecular process may have deep implications in the management of bladder cancer patients and in the design of novel molecularly targeted therapeutic approaches.
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Registered trials
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.