ArticleMolecular oncology2012
CRABP-II methylation: a critical determinant of retinoic acid resistance of medulloblastoma cells.
Article in Molecular oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- RETRACTED: Maggot extract accelerates skin wound healing of diabetic rats via enhancing STAT3 signaling.PloS one · 2024Article
- Temozolomide Resistance in Glioblastoma by NRF2: Protecting the Evil.Biomedicines · 2023Review
- [Research Progress of DNA Methylation in Cisplatin Resistance in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Review
- Super-enhancer associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells.Frontiers in cell and developmental biology · 2022Article
- Development and validation of the prognostic value of the immune-related genes in clear cell renal cell carcinoma.Translational andrology and urology · 2021Article
- Resveratrol Reverses Retinoic Acid Resistance of Anaplastic Thyroid Cancer Cells via Demethylating CRABP2 Gene.Frontiers in endocrinology · 2019Article
- A panel of biomarkers for skin squamous cell carcinoma: various functional entities and differential responses to resveratrol.International journal of clinical and experimental pathology · 2019Article
- UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts.Journal of neuro-oncology · 2018Article
- Differential CRABP-II and FABP5 expression patterns and implications for medulloblastoma retinoic acid sensitivity.RSC advances · 2018Article
- Resveratrol Suppresses the Growth and Enhances Retinoic Acid Sensitivity of Anaplastic Thyroid Cancer Cells.International journal of molecular sciences · 2018Article
- Why Differentiation Therapy Sometimes Fails: Molecular Mechanisms of Resistance to Retinoids.International journal of molecular sciences · 2018Review
- Correlation of ARHI upregulation with growth suppression and STAT3 inactivation in resveratrol-treated ovarian cancer cells.Cancer biomarkers : section A of Disease markers · 2018Article
- 4-Amino-2-trifluoromethyl-phenyl retinate inhibits proliferation, invasion, and migration of breast cancer cells by independently regulating CRABP2 and FABP5.Drug design, development and therapy · 2018Article
- All-trans retinoic acid enhances temozolomide-induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway.Oncology letters · 2017Article
- MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro.PloS one · 2017Article
- SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling.Nutrients · 2016Article
- Enhanced inhibition of clonogenic survival of human medulloblastoma cells by multimodal treatment with ionizing irradiation, epigenetic modifiers, and differentiation-inducing drugs.Journal of experimental & clinical cancer research : CR · 2016Article
- Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.PloS one · 2016Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medulloblastoma cells exhibit varied responses to therapy by all-trans retinoic acid (RA). The underlying mechanism for such diverse effects however remains largely unclear. In this study, we attempted to elucidate the molecular basis of RA resistance through the study of RA signaling components in both RA-sensitive (Med-3) and RA-resistant (UW228-2 and UW228-3) medulloblastoma cells. The results revealed that RARα/β/γ and RXRα/β/γ were found in the three cell lines. Expression of CRABP-I and CRABP-II was seen in Med-3 cells, up-regulated when treated with RA, but was absent in UW228-2 and UW228-3 cells regardless of RA treatment. Bisulfite sequencing revealed 8 methylated CG sites at the promoter region of CRABP-II in UW228-2 and UW228-3 but not in Med-3 cells. Demethylation by 5-aza-2'-deoxycytidine recovered CRABP-II expression. Upon restoration of CRABP-II expression, both UW228-2 and UW228-3 cells responded to RA treatment by forming neuronal-like differentiation, synaptophysin expression, β-III tubulin upregulation, and apoptosis. Furthermore, CRABP-II specific siRNA reduced RA sensitivity in Med-3 cells. Tissue microarray-based immunohistochemical staining showed variable CRABP-II expression patterns among 104 medulloblastoma cases, ranging from negative (42.3%), partly positive (14.4%) to positive (43.3%). CRABP-II expression was positively correlated with synaptophysin (rs = 0.317; p = 0.001) but not with CRABP-I expression (p > 0.05). In conclusion, aberrant methylation in CRABP-II reduces the expression of CRABP-II that in turn confers RA resistance in medulloblastoma cells. Determination of CRABP-II expression or methylation status may enable a personalized RA therapy in patients with medulloblastomas and other types of cancers.
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