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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect glioblastoma cell viability
1Department of Neurosurgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, China.
Abstract:
Dysregulation of pseudogenes is involved in the progression of various types of cancer, including glioblastoma (GBM). Proliferation associated-2G4 (PA2G4) pseudogene 4 (PA2G4P4) has been shown to play an oncogenic role in bladder cancer development. Our study aimed to explore the role and mechanism of PA2G4P4 in GBM progression. PA2G4P4 and PA2G4 expression in GBM tissues was analyzed using the GEPIA database. Cell viability, apoptosis, and activities of caspase-3 and caspase-9 in GBM cells were explored by CCK-8, flow cytometry analysis, and colorimetric activity assay kits, respectively. GEPIA database showed that PA2G4P4 and PA2G4 were both upregulated in GBM tissues. PA2G4P4 expression was also boosted in GBM cells. Knockdown of PA2G4P4 or PA2G4 inhibited cell viability, induced apoptosis, and increased caspase-3 and caspase-9 activities in GBM cells. Data from UALCAN database showed that among top 15 genes correlated with PA2G4P4, PA2G4 had the highest correlation coefficient. Additionally, knockdown of PA2G4P4 inhibited PA2G4 expression and nuclear translocation in GBM cells. Overexpression of PA2G4 abolished the functions of PA2G4P4 knockdown on viability and apoptosis in GBM cells. Summarily, pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect cell viability and apoptosis in GBM cells.
Insights
Pseudogene PA2G4P4 promotes glioblastoma (GBM) progression by increasing oncogene PA2G4 expression and nuclear translocation. This impacts GBM cell viability and apoptosis, highlighting PA2G4P4 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pseudogene dysregulation is implicated in cancer development.
- PA2G4P4 has an oncogenic role in bladder cancer.
- Glioblastoma (GBM) is an aggressive brain tumor where pseudogene roles are under investigation.
Purpose of the Study:
- To investigate the role and mechanism of PA2G4P4 in GBM progression.
- To determine the relationship between PA2G4P4 and PA2G4 in GBM.
- To assess the impact of PA2G4P4 on GBM cell behavior.
Main Methods:
- Analysis of PA2G4P4 and PA2G4 expression in GBM tissues using the GEPIA database.
- Assessment of GBM cell viability, apoptosis, and caspase activity via CCK-8, flow cytometry, and activity assay kits.
- Gene knockdown and overexpression experiments to elucidate functional mechanisms.
Main Results:
- PA2G4P4 and PA2G4 were found to be upregulated in GBM tissues and cells.
- Knockdown of PA2G4P4 or PA2G4 inhibited GBM cell viability and induced apoptosis.
- PA2G4P4 knockdown reduced PA2G4 expression and nuclear translocation; PA2G4 overexpression rescued PA2G4P4 knockdown effects.
Conclusions:
- Pseudogene PA2G4P4 promotes GBM progression by enhancing oncogene PA2G4 expression and nuclear translocation.
- PA2G4P4 influences GBM cell viability and apoptosis.
- PA2G4P4 represents a potential therapeutic target for glioblastoma.
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