ArticleJournal of experimental & clinical cancer research : CR2017
Hypermethylation and loss of retinoic acid receptor responder 1 expression in human choriocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 39 citations in OpenAlex.
- Identification of cancer-associated fibroblast signature genes for potential biomarkers in cholangiocarcinoma: a Mendelian randomization study.Discover oncology · 2025Article
- RARRES1 attenuates HFrontiers in physiology · 2025Article
- Genetic and histological analysis intraplacental choriocarcinoma: a case report.Medical molecular morphology · 2024Article
- RARRES1 inhibits hepatocellular carcinoma progression and increases its sensitivity to lenvatinib through interaction with SPINK2.Biology direct · 2024Article
- The Contribution of Hippocampal All-Trans Retinoic Acid (ATRA) Deficiency to Alzheimer's Disease: A Narrative Overview of ATRA-Dependent Gene Expression in Post-Mortem Hippocampal Tissue.Antioxidants (Basel, Switzerland) · 2023Review
- Establishment of an ovarian cancer omentum metastasis-related prognostic model by integrated analysis of scRNA-seq and bulk RNA-seq.Journal of ovarian research · 2022Article
- Interaction of RARRES1 with ICAM1 modulates macrophages to suppress the progression of kidney renal clear cell carcinoma.Frontiers in immunology · 2022Article
- Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity.Archives of gynecology and obstetrics · 2021Article
- Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach.Frontiers in cell and developmental biology · 2021Article
- Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells.Cell biochemistry and biophysics · 2020Article
- Expression of Retinoid Acid Receptor-Responsive Genes in Rodent Models of Placental Pathology.International journal of molecular sciences · 2019Article
- The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia.EBioMedicine · 2018Article
- Tumor suppressor RARRES1- A novel regulator of fatty acid metabolism in epithelial cells.PloS one · 2018Article
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
backgroundHuman placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and temporal regulation is thought to contribute to the rare formation of choriocarcinomas. Promoter hypermethylation and loss of the tumor suppressor Retinoic acid receptor responder 1 (RARRES1) were shown to contribute to cancer progression. Our study investigated the epigenetic and transcriptional regulation of RARRES1 in healthy human placenta in comparison to choriocarcinoma cell lines and cases.
methodsThree choriocarcinoma cell lines (Jeg-3, JAR and BeWo) were treated with three different retinoic acid derivates (Am580, Tazarotene and all-trans retinoic acid) and 5-aza-2'-deoxycytidine. We analyzed RARRES1 promoter methylation by pyrosequencing and performed realtime-PCR quantification to determine RARRES1 expression in placental tissue and trophoblastic cell lines. Additionally, RARRES1 was stained in healthy placentas and in biopsies of choriocarcinoma cases (n = 10) as well as the first trimester trophoblast cell line Swan71 by immunofluorescence and immunohistochemistry.
resultsIn the choriocarcinoma cell lines, RARRES1 expression could not be induced by sole retinoic acid treatment. Stimulation with 5-aza-2'-deoxycytidine significantly induced RARRES1 expression, which then could be further increased with Am580, Tazarotene and all-trans retinoic acid. In comparison to healthy placenta, choriocarcinoma cell lines showed a hypermethylation of the RARRES1 promoter, which correlated with a reduced RARRES1 expression. In concordance, RARRES1 protein expression was lost in choriocarcinoma tissue. Additionally, in the trophoblastic cell line Swan71, we found a significant induction of RARRES1 expression with increased cell density, during mitosis and in syncytial knots.
conclusionsOur findings showed that RARRES1 expression is absent in choriocarcinoma due to promoter methylation. Based on our analysis, we hypothesize that RARRES1 might exert tumor suppressive functions in multiple cellular processes (e.g. cell cycle regulation, adhesion, invasion and apoptosis).
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