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Published on: April 24, 2021
PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway
Guanghui Bi1, Jingfeng Yan2, Shuzhen Sun3
1Department of Neurology, Dong Ying People's Hospital, Dongying City 257091, Shan dong Province, PR China.
Abstract:
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention.
Insights
Proline-rich transmembrane protein 2 (PRRT2) acts as a tumor suppressor in glioma. Its down-regulation, influenced by microRNA-30a-5p, promotes glioma cell viability and inhibits apoptosis, suggesting PRRT2 as a therapeutic target.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene are linked to paroxysmal neurological disorders.
- The role of PRRT2 in cancer, specifically glioma, remains largely unexplored.
Purpose of the Study:
- To investigate the function of PRRT2 in glioma tumorigenesis.
- To elucidate the regulatory mechanisms and therapeutic potential of PRRT2 in glioma.
Main Methods:
- Large-scale data analysis of PRRT2 expression in glioma tissues versus normal brain tissue.
- Investigation of PRRT2 regulation by microRNA-30a-5p, mutations, copy number variations, and epigenetic modifications.
- Cell viability and apoptosis assays following PRRT2 overexpression, with and without microRNA-30a-5p modulation.
- Analysis of PRRT2's correlation with genes in the unfolded protein response (UPR) pathway.
Main Results:
- PRRT2 is significantly down-regulated in glioma tissues compared to normal brain tissue.
- PRRT2 dysregulation is modulated by microRNA-30a-5p, not by mutation, copy number variation, or epigenetic changes.
- Overexpression of PRRT2 inhibits glioma cell viability and promotes apoptosis, effects reversible by microRNA-30a-5p.
- PRRT2 expression correlates with genes in the UPR pathway, and its introduction inhibits UPR signaling.
Conclusions:
- PRRT2 functions as a tumor suppressor in glioma.
- PRRT2's anti-tumor effects are mediated through the modulation of the UPR pathway.
- PRRT2 represents a potential therapeutic target for glioma treatment.
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