ArticleEpigenetics2014
microRNA-199a-3p, DNMT3A, and aberrant DNA methylation in testicular cancer.
Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Mechanisms of DNMT3A-3L-mediated de novo DNA methylation on chromatin.Nature structural & molecular biology · 2026Article
- Comprehensive analysis of microRNA expression provides mechanistic insights into transcriptomic alteration in primary and metastatic testicular germ cell tumors.Scientific reports · 2025Article
- M2 Macrophage-Derived Exosomes Regulate miR-199a-3p Promoter Methylation Through the LINC00470-Mediated myc/DNMT3a Axis to Promote Breast Cancer Development.Biochemical genetics · 2024Article
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma.Journal of translational medicine · 2024Article
- Epigenetic Factors and ncRNAs in Testicular Cancer.International journal of molecular sciences · 2023Review
- miRNA in Molecular Diagnostics.Bioengineering (Basel, Switzerland) · 2022Review
- HOTAIR/Sp1/miR-199a critically regulates cancer stemness and malignant progression of cutaneous squamous cell carcinoma.Oncogene · 2022Article
- The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia.Frontiers in molecular neuroscience · 2022Review
- Methylation geneOncology reports · 2021Article
- Epigenetic alterations as therapeutic targets in Testicular Germ Cell Tumours : current and future application of 'epidrugs'.Epigenetics · 2021Review
- Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy.Cancer gene therapy · 2021Review
- MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.Acta neuropathologica · 2021Article
- Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-β1 Activity That Regulates Fibrosis in Crohn's Disease.Inflammatory bowel diseases · 2020Article
- Review
- The Suppression of miR-199a-3p by Promoter Methylation Contributes to Papillary Thyroid Carcinoma Aggressiveness by Targeting RAP2a and DNMT3a.Frontiers in cell and developmental biology · 2020Article
- Exploration and validation of downregulated microRNA-199a-3p, downstream messenger RNA targets and transcriptional regulation in osteosarcoma.American journal of translational research · 2019Article
- The Role of DNA/Histone Modifying Enzymes and Chromatin Remodeling Complexes in Testicular Germ Cell Tumors.Cancers · 2018Review
- Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation.Molecular carcinogenesis · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It was previously demonstrated that miR-199a was downregulated in testicular germ cell tumor (TGCT), probably due to hypermethylation of its promoter. Further study found that re-expression of miR-199a in testicular cancer cells (NT2) led to suppression of cell growth, cancer migration, invasion and metastasis. More detailed analyses showed that these properties of miR-199a could be assigned to miR-199a-5p, one of its two derivatives. The biological role of the other derivative, miR-199a-3p in TGCT, remains largely uncharacterized. In this report, we identified DNA (cytosine-5)-methyltransferase 3A (DNMT3A), the de novo methyltransferase, as a direct target of miR-199a-3p using a 3'-UTR reporter assay. Transient expression of miR-199a-3p in NT2 cells led to decrease, while knocking down of miR-199a-3p in a normal human testicular cell line (HT) led to elevation, of DNMT3A2 (DNMT3A gene isoform 2) mRNA and protein levels. In clinical samples, DNMT3A2 was significantly overexpressed in malignant testicular tumor, and the expression of DNMT3A2 was inversely correlated with the expression of miR-199a-3p. However, DNMT3A did not affect miR-199a expression in NT2 cells. Further characterization of miR-199a-3p revealed that it negatively regulated DNA methylation, partly through targeting DNMT3A. Overexpression of miR-199a-3p restored the expression of APC and MGMT tumor-suppressor genes in NT2 cells by affecting DNA methylation of their promoter regions. Our studies demonstrated the deregulation of miR-199a-3p expression in TGCT may provide novel mechanistic insights into TGCT carcinogenesis and suggested a potentially therapeutic use of synthetic miR-199a-3p oligonucleotides as effective hypomethylating compounds in the treatment of TGCT.
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