ArticlePloS one2010
Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Shared Mechanisms inPPAR research · 2024Article
- The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders.International journal of molecular sciences · 2021Review
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- Peroxisome proliferator-activated receptor gamma as a theragnostic target for mesenchymal-type glioblastoma patients.Experimental & molecular medicine · 2020Article
- Aberrant Expression of Peroxisome Proliferator-Activated Receptors in Colorectal Cancer and Their Association with Cancer Progression and Prognosis.Gastrointestinal tumors · 2020Article
- PPARG expression in colorectal cancer and its association with staging and clinical evolution.Acta cirurgica brasileira · 2020Article
- Article
- DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications.Frontiers in oncology · 2019Review
- Article
- Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile.Scientific reports · 2018Article
- Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics.Scientific reports · 2017Article
- Aberrant BLM cytoplasmic expression associates with DNA damage stress and hypersensitivity to DNA-damaging agents in colorectal cancer.Journal of gastroenterology · 2017Article
- MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers.PPAR research · 2017Review
- Proteomic characterization of peroxisome proliferator-activated receptor-γ (PPARγ) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype.Molecular oncology · 2016Article
- Article
- Commonalities in the Association between PPARG and Vitamin D Related with Obesity and Carcinogenesis.PPAR research · 2016Review
- Perinatal nicotine exposure suppresses PPARγ epigenetically in lung alveolar interstitial fibroblasts.Molecular genetics and metabolism · 2015Article
- Chemotherapy and chemoprevention by thiazolidinediones.BioMed research international · 2015Review
- Nuclear receptors and epigenetic regulation: opportunities for nutritional targeting and disease prevention.Advances in nutrition (Bethesda, Md.) · 2014Review
Corrections and comments
- Retraction · 2019-12-27Concerns/Issues about Image ·
- Erratum issued
- Retracted
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The relationship between peroxisome proliferator-activated receptor γ (PPARG) expression and epigenetic changes occurring in colorectal-cancer pathogenesis is largely unknown. We investigated whether PPARG is epigenetically regulated in colorectal cancer (CRC) progression. PPARG expression was assessed in CRC tissues and paired normal mucosa by western blot and immunohistochemistry and related to patients' clinicopathological parameters and survival. PPARG promoter methylation was analyzed by methylation-specific-PCR and bisulphite sequencing. PPARG expression and promoter methylation were similarly examined also in CRC derived cell lines. Chromatin immunoprecipitation in basal conditions and after epigenetic treatment was performed along with knocking-down experiments of putative regulatory factors. Gene expression was monitored by immunoblotting and functional assays of cell proliferation and invasiveness. Methylation on a specific region of the promoter is strongly correlated with PPARG lack of expression in 30% of primary CRCs and with patients' poor prognosis. Remarkably, the same methylation pattern is found in PPARG-negative CRC cell lines. Epigenetic treatment with 5'-aza-2'-deoxycytidine can revert this condition and, in combination with trichostatin A, dramatically re-activates gene transcription and receptor activity. Transcriptional silencing is due to the recruitment of MeCP2, HDAC1 and EZH2 that impart repressive chromatin signatures determining an increased cell proliferative and invasive potential, features that can experimentally be reverted. Our findings provide a novel mechanistic insight into epigenetic silencing of PPARG in CRC that may be relevant as a prognostic marker of tumor progression.
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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.