Related Experiment Video
Updated: Jun 16, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
PTBP1 acts as a tumor suppressor in glioma by promoting HMOX1-dependent ferroptosis
Jing Sun1, Bing Xue2, Tingkai Sun2
1Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang 212013, PR China; Department of Traditional Chinese Medicine & Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, PR China.
Abstract:
Glioblastoma (GBM) is the most common glioma with a 5-year relative survival rate of only 5%. Gliomas progress diffusely despite treatment, and all glioblastomas eventually progress or recur following traditional radiotherapy and chemotherapy. Therefore, targeted therapy is particularly important for gliomas. Several studies have shown that the expression of polypyrimidine tract-binding protein 1 (PTBP1) is critical for glioma development. However, the exact molecular mechanisms remain unknown. Here, we performed transcriptome sequencing in glioma cells with or without inhibiting PTBP1 to uncover the underlying mechanisms, followed by in vitro and in vivo functional validation. We found that PTBP1 knockdown (KD) promotes ferroptosis by upregulating the expression of heme oxygenase 1 (HMOX1), while ferrostatin-1 (Fer-1), deferoxamine (DFOM) or si-HMOX1 effectively block PTBP1 deletion-mediated ferroptosis pathway activation. Importantly, we also use high-grade glioma cells for orthotopic transplantation aimed at validating PTBP1/ HMOX1 pathway in vivo, and confirmed that PTBP1 knockdown induced ferroptosis in glioma cells through the upregulation of HMOX1. This study uncovers a novel mechanistic understanding of the role of PTBP1 in glioma development, which constitutes a novel biomarker and target for GBM.
Insights
Polypyrimidine tract-binding protein 1 (PTBP1) knockdown promotes ferroptosis in glioblastoma by increasing heme oxygenase 1 (HMOX1). This PTBP1/HMOX1 pathway offers a new therapeutic target for glioblastoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastoma (GBM) has a poor prognosis, with a 5-year survival rate of only 5%.
- Current treatments like radiotherapy and chemotherapy are often insufficient, as gliomas recur or progress.
- Targeted therapies are crucial for improving GBM outcomes, yet underlying mechanisms require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which polypyrimidine tract-binding protein 1 (PTBP1) influences glioma development.
- To identify novel therapeutic targets for glioblastoma.
Main Methods:
- Transcriptome sequencing was performed on glioma cells with and without PTBP1 inhibition.
- In vitro and in vivo functional validations were conducted.
- Orthotopic transplantation models using high-grade glioma cells were employed.
Main Results:
- PTBP1 knockdown (KD) was found to promote ferroptosis in glioma cells.
- This effect was mediated by the upregulation of heme oxygenase 1 (HMOX1) expression.
- Inhibition of ferroptosis using ferrostatin-1 (Fer-1), deferoxamine (DFOM), or si-HMOX1 blocked the PTBP1 KD-induced ferroptosis pathway.
- In vivo studies confirmed that PTBP1 KD induces ferroptosis via HMOX1 upregulation in an orthotopic glioma model.
Conclusions:
- PTBP1 plays a critical role in glioma development through the regulation of ferroptosis.
- The PTBP1/HMOX1 pathway represents a novel mechanistic insight into glioblastoma.
- PTBP1 and HMOX1 are potential biomarkers and therapeutic targets for glioblastoma.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:23Abnormal Proliferation
01:24Regulation of Angiogenesis and Blood Supply
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...