ArticleMolecular biology of the cell2015
Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK).
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Midkine and pleiotrophin in glioma: From mechanistic insights to therapeutic potential.Neoplasia (New York, N.Y.) · 2026Review
- Identification of the promoter region of the human P2RX7 gene.Purinergic signalling · 2026Article
- Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.Cancer letters · 2026Review
- Unraveling the Role of MDK-SDC4 Interaction in Pancreatic Cancer-Associated New-Onset Diabetes by Single-Cell Transcriptomic Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Midkine (MDK) in cancer and drug resistance: from inflammation to therapy.Discover oncology · 2025Review
- Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma.Clinical and translational medicine · 2025Article
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- Multi-scale signaling and tumor evolution in high-grade gliomas.Cancer cell · 2024Article
- C-Myc/H19/miR-29b axis downregulates nerve/glial (NG)2 expression in glioblastoma multiforme.Molecular therapy. Nucleic acids · 2024Article
- Identification ofBiomedicines · 2024Article
- Sp1 Upregulation Bolsters the Radioresistance of Glioblastoma Cells by Promoting Double Strand Breaks Repair.International journal of molecular sciences · 2023Article
- Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting.International journal of molecular sciences · 2023Review
- Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment.Nature communications · 2022Article
- Sp1 induced gene TIMP1 is related to immune cell infiltration in glioblastoma.Scientific reports · 2022Article
- Insulin-Like Growth Factor 1 Receptor Drives Hepatocellular Carcinoma Growth and Invasion by Activating Stat3-Midkine-Stat3 Loop.Digestive diseases and sciences · 2022Article
- Identification of a Five-mRNA Signature as a Novel Potential Prognostic Biomarker for Glioblastoma by Integrative Analysis.Frontiers in genetics · 2022Article
- Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes.International journal of molecular sciences · 2021Article
- Down-regulation of the Sp1 transcription factor by an increase of microRNA-4497 in human placenta is associated with early recurrent miscarriage.Reproductive biology and endocrinology : RB&E · 2021Article
- Differentiated embryonic chondrocyte-expressed gene 1 promotes temozolomide resistance by modulating the SP1-MGMT axis in glioblastoma.American journal of translational research · 2021Article
- Synergistic regulation of methylation and SP1 on MAGE-D4 transcription in glioma.American journal of translational research · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. However, the upstream signaling that leads to MDK accumulation remains elusive. This study investigates the molecular mechanism that induces MDK overexpression in human glioma. The Repository for Molecular Brain Neoplasia Data was analyzed to identify potential MDK regulators. Expression of MDK and specificity protein 1 (SP1) was compared in glioma specimens. Chromatin immunoprecipitation assay was used to confirm the transcriptional regulation. MDK-force-expressed, SP1-silenced glioma cells were used to test rescue effects in vitro and in vivo. MDK and SP1 expression in gliomas was significantly higher than in adjacent tissues and was positively correlated in glioma clinical samples and cell lines. The promoter of the human MDK gene has a putative SP1 binding site. SP1 binds to the promoter of the MDK gene and directly regulates MDK expression. MDK or SP1 gene silencing inhibited the proliferation of glioma cells and reduced the tumor volume in nude mice. Overexpression of MDK in SP1-silenced cells could partially rescue the SP1 inhibition effects in vivo and in vitro. SP1 directly up-regulated the expression of MDK, and the SP1-MDK axis cooperated in glioma tumorigenesis.
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