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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Sun, Qian Xu, Yang Yuan, Fan’en Qi, Yangzhi Wang, Yixuan Chen, Qianxue Liu, Baohui |
| Abstract | Background Ferroptosis is an iron dependent cell death closely associated with p53 signaling pathway and is aberrantly regulated in glioblastoma (GBM), yet the underlying mechanism needs more exploration. Identifying new factors which regulate p53 and ferroptosis in GBM is essential for treatment. Methods Glioma cell growth was evaluated by cell viability assays and colony formation assays. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays, and transmission electron microscopy were used to assess the degree of cellular lipid peroxidation of GBM. The mechanisms of RND1 in regulation of p53 signaling were analyzed by RT-PCR, western blot, immunostaining, co-immunoprecipitation, ubiquitination assays and luciferase reporter assays. The GBM‐xenografted animal model was constructed and the tumor was captured by an In Vivo Imaging System (IVIS). Results From the The Cancer Genome Atlas (TCGA) database, we summarized that Rho family GTPase 1 (RND1) expression was downregulated in GBM and predicted a better prognosis of patients with GBM. We observed that RND1 influenced the glioma cell growth in a ferroptosis-dependent manner when GBM cell lines U87 and A172 were treated with Ferrostatin-1 or Erastin. Mechanistically, we found that RND1 interacted with p53 and led to the de-ubiquitination of p53 protein. Furthermore, the overexpression of RND1 promoted the activity of p53-SLC7A11 signaling pathway, therefore inducing the lipid peroxidation and ferroptosis of GBM. Conclusions We found that RND1, a novel controller of p53 protein and a positive regulator of p53 signaling pathway, enhanced the ferroptosis in GBM. This study may shed light on the understanding of ferroptosis in GBM cells and provide new therapeutic ideas for GBM. |
| Related Links | https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-022-00791-w.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20453701 |
| DOI | 10.1186/s13578-022-00791-w |
| Journal | Cell & Bioscience |
| Issue Number | 1 |
| Volume Number | 12 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-05-03 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Microbiology Stem Cells Neurobiology Proteomics RND1 p53 Ferroptosis GBM |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 7/2023 |
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