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Updated: Jun 30, 2025
Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
Dioscin decreases M2 polarization via inhibiting a positive feedback loop between RBM47 and NF-κB in glioma
Jialing Bai1, Xinxiang Zhang1, Wanyao Meng1
1Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, PR China.
Background:
The role of the glioblastoma (GBM) microenvironment is pivotal in the development of gliomas. Discovering drugs that can traverse the blood-brain barrier and modulate the tumor microenvironment is crucial for the treatment of GBM. Dioscin, a steroidal saponin derived from various kinds of plants and herbs known to penetrate the blood-brain barrier, has shown its powerful anti-tumor activity. However, little is known about its effects on GBM microenvironment.
Methods:
Bioinformatics analysis was conducted to assess the link between GBM patients and their prognosis. Multiple techniques, including RNA sequencing, immunofluorescence staining, Western blot analysis, RNA-immunoprecipitation (RIP) assays, and Chromatin immunoprecipitation (CHIP) analysis were employed to elucidate the mechanism through which Dioscin modulates the immune microenvironment.
Results:
Dioscin significantly impaired the polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages in vitro and in vivo. A strong correlation between high expression of RBM47 in GBM and a detrimental prognosis for patients was demonstrated. RNA-sequencing analysis revealed an association between RBM47 and the immune response. The inhibition of RBM47 significantly impaired the recruitment and polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages. Moreover, RBM47 could stabilize the mRNA of inflammatory genes and enhance the expression of these genes by activating the NF-κB pathway. In addition, NF-κB acts as a transcription factor that enhances the transcriptional activity of RBM47. Notably, we found that Dioscin could significantly inhibit the activation of NF-κB and then downregulate the expression of RBM47 and inflammatory genes protein.
Conclusion:
Our study reveals that the positive feedback loop between RBM47 and NF-κB could promote immunosuppressive microenvironment in GBM. Dioscin effectively inhibits M2 polarization in GBM by disrupting the positive feedback loop between RBM47 and NF-κB, indicating its potential therapeutic effects in GBM treatment.
Insights
Dioscin, a natural compound, combats glioblastoma (GBM) by targeting the RBM47-NF-κB feedback loop. This disrupts the immunosuppressive tumor microenvironment, offering potential new GBM therapies.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Glioblastoma (GBM) microenvironment critically influences tumor progression.
- Targeting the blood-brain barrier with novel therapeutics is essential for GBM treatment.
- Dioscin, a plant-derived saponin, penetrates the blood-brain barrier and exhibits anti-tumor properties, but its impact on the GBM microenvironment is unclear.
Purpose of the Study:
- To investigate the effects of Dioscin on the glioblastoma microenvironment.
- To elucidate the molecular mechanisms underlying Dioscin's anti-tumor activity in GBM.
- To explore the role of RBM47 and NF-κB in GBM immunosuppression and their modulation by Dioscin.
Main Methods:
- Bioinformatics analysis of GBM patient data and prognosis.
- In vitro and in vivo assessment of macrophage polarization and phagocytosis.
- RNA sequencing, immunofluorescence, Western blot, RIP, and CHIP assays to determine molecular mechanisms.
- Investigation of the RBM47-NF-κB pathway and its regulation by Dioscin.
Main Results:
- Dioscin inhibited M2 macrophage polarization and enhanced macrophage phagocytosis in GBM.
- High RBM47 expression correlated with poor GBM patient prognosis and was linked to immune response.
- Dioscin disrupted the RBM47-NF-κB positive feedback loop, downregulating inflammatory gene expression and protein levels.
- RBM47 stabilizes inflammatory gene mRNA via NF-κB activation, contributing to an immunosuppressive GBM microenvironment.
Conclusions:
- A positive feedback loop between RBM47 and NF-κB promotes an immunosuppressive GBM microenvironment.
- Dioscin effectively inhibits M2 polarization in GBM by disrupting this RBM47-NF-κB loop.
- Dioscin demonstrates significant therapeutic potential for GBM treatment by modulating the tumor immune microenvironment.
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