ArticleJournal of experimental & clinical cancer research : CR2019
miR-504 suppresses mesenchymal phenotype of glioblastoma by directly targeting the FZD7-mediated Wnt-β-catenin pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- GPCR signaling systems facilitate precision interventions for multi-oncology therapy.Frontiers in systems biology · 2026Review
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.Molecular cancer · 2025Review
- Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition.Cancer biology & medicine · 2024Review
- Integrative multi-omics characterization reveals sex differences in glioblastoma.Biology of sex differences · 2024Article
- Review
- A complex of Wnt/planar cell polarity signaling components Vangl1 and Fzd7 drives glioblastoma multiforme malignant properties.Cancer letters · 2023Article
- microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)-Recent Literature Review.International journal of molecular sciences · 2023Review
- The miR-3648/FRAT1-FRAT2/c-Myc negative feedback loop modulates the metastasis and invasion of gastric cancer cells.Oncogene · 2022Article
- miR-637 Prevents Glioblastoma Progression by Interrupting ZEB2/WNT/β-catenin Cascades.Cellular and molecular neurobiology · 2022Article
- Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma.Cells · 2022Article
- Article
- Review
- 4,5-Dimethoxycanthin-6-one is a novel LSD1 inhibitor that inhibits proliferation of glioblastoma cells and induces apoptosis and pyroptosis.Cancer cell international · 2022Article
- WNT signaling at the intersection between neurogenesis and brain tumorigenesis.Frontiers in molecular neuroscience · 2022Review
- MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes.Molecular medicine (Cambridge, Mass.) · 2021Article
- The direct miR-874-3p-target FAM84A promotes tumor development in papillary thyroid cancer.Molecular oncology · 2021Article
- Glioblastoma and MiRNAs.Cancers · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroRNAs (miRNAs) play crucial roles in tumor initiation and development. Previously, we indicated that miR-504 is downregulated and suppresses tumor proliferation in glioblastoma (GBM). However, the regulation and relevant mechanism of miR-504 in GBM mesenchymal (ME) transition remain unclear.
methodsTranscriptome and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. The potential functions of miR-504 were predicted using gene ontology analysis. GBM cell migration and invasion were examined using wound healing and Transwell assays. Epithelial-mesenchymal transition (EMT) progression in GBM cell lines was detected with immunofluorescence and western blotting. The stemness activity of glioma stem-like cells (GSCs) was assessed by sphere formation assay and tumor xenograft model. miR-504 binding to the FZD7 (frizzled class receptor 7) 3' untranslated region (3'UTR) was validated using dual luciferase reporter assay. TOP/FOP Flash assays were conducted to determine the effects of miR-504 on Wnt/β-catenin signaling.
resultsAnalysis of TCGA transcriptomic data showed that low miR-504 expression correlated with ME subtype transition and poor survival in patients with GBM. Functional experiments showed that miR-504 overexpression suppressed malignant behaviors of GBM cells, such as migration, invasion, EMT, and stemness activity. Furthermore, miR-504 was a negative regulator of the Wnt-β-catenin pathway by directly repressing FZD7 expression, and FZD7 overexpression reversed the EMT inhibition caused by miR-504. Moreover, the low miR-504/FZD7 expression ratio was a ME subtype marker and could serve as a significant prognostic indicator and predict the clinical outcome of chemotherapy and radiotherapy for patients with GBM in TCGA dataset.
conclusionsOur results suggest that miR-504 suppresses the aggressive biological processes associated with the ME phenotype of GBM and could be a potential candidate for therapeutic applications in these malignant brain tumors.
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