ArticleMolecular & cellular proteomics : MCP2015
Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells.
Article in Molecular & cellular proteomics : MCP, 2015. 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, 67 citations in OpenAlex.
- Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways.Biogerontology · 2026Review
- Flavonoids and miRNA Modulation: A Novel Approach to Managing Cancer, Diabetes, Depression, and Neurological Disorders.BioMed research international · 2026Review
- Plant bioactive compounds driven microRNAs (miRNAs): A potential source and novel strategy targeting gene and cancer therapeutics.Non-coding RNA research · 2024Article
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
- Resveratrol Induces Autophagy and Apoptosis in Non-Small-Cell Lung Cancer Cells by Activating the NGFR-AMPK-mTOR Pathway.Nutrients · 2022Article
- Implication of the Mediterranean diet on the human epigenome.Journal of preventive medicine and hygiene · 2022Review
- The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets.Biomarker research · 2022Review
- Mass spectrometric investigations of caloric restriction mimetics.Proteomics · 2021Review
- Non-Coding RNAs Participate in the Pathogenesis of Neuroblastoma.Frontiers in oncology · 2021Review
- MicroRNA 449c Mediates the Generation of Monocytic Myeloid-Derived Suppressor Cells by Targeting STAT6.Molecules and cells · 2020Article
- MicroRNAs: Diverse Mechanisms of Action and Their Potential Applications as Cancer Epi-Therapeutics.Biomolecules · 2020Review
- miR-137: A Novel Therapeutic Target for Human Glioma.Molecular therapy. Nucleic acids · 2020Review
- Low expression levels of plasma miR-141 are associated with susceptibility to gastric cancer.Oncology letters · 2019Article
- Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.Frontiers in oncology · 2019Review
- MiR-137 Deficiency Causes Anxiety-Like Behaviors in Mice.Frontiers in molecular neuroscience · 2019Article
- MicroRNAs in neuroblastoma tumorigenesis, therapy resistance, and disease evolution.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Regulatory characterisation of the schizophrenia-associated CACNA1C proximal promoter and the potential role for the transcription factor EZH2 in schizophrenia aetiology.Schizophrenia research · 2018Article
- A comprehensive review of the genetic and biological evidence supports a role for MicroRNA-137 in the etiology of schizophrenia.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2018Review
- MicroRNA‑137 has a suppressive role in liver cancer via targeting EZH2.Molecular medicine reports · 2017Article
- miR-449a inhibits colorectal cancer progression by targeting SATB2.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma is the most common pediatric extracranial solid tumor with a broad spectrum of clinical behavior and poor prognosis. Despite intensive multimodal therapy, ongoing clinical trials, and basic science investigations, neuroblastoma remains a complex medical challenge with a long-term survival rate less than 40%. In our study, we found that resveratrol (3, 5, 4'-trihydroxystilbene, RSV), a naturally occurring phytoalexin, possesses an anticancer activity through blocking cell growth and inducing apoptosis in neuroblastoma cell line Neuro-2a (N-2a) cells. Using stable isotope labeling with amino acids in cell culture (SILAC) and quantitative proteomic analysis, we found that 395 proteins were up-regulated and 302 proteins were down-regulated in the nucleus of N-2a cells treated with RSV. Among these, the polycomb protein histone methyltransferase EZH2 was reduced significantly, which is aberrantly overexpressed in neuroblastoma and crucial to maintain the malignant phenotype of neuroblastoma by epigenetic repression of multiple tumor suppressor genes. EZH2 reduction further led to decreased H3K27me3 level and reactivation of neuroblastoma tumor suppressor genes CLU and NGFR. Disruption EZH2 expression by RNA interference-mediated knockdown or pharmacologic inhibition with DZNep triggered cellular apoptosis in N-2a cells. We found that the up-regulation of miR-137 level was responsible for reduced EZH2 level in tumor suppression induced by RSV. Inhibition of miR-137 expression rescued the cellular apoptosis phenotypes, EZH2 reduction, and CLU and NGFR reactivation, associated with RSV treatment. Taken together, our findings present for the first time, an epigenetic mechanism involving miR-137-mediated EZH2 repression in RSV-induced apoptosis and tumor suppression of neuroblastoma, which would provide a key potential therapeutic target in neuroblastoma treatment.
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