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RETRACTED: Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines
Sahar Safaee1, Masoumeh Fardi1,2, Nima Hemmat1
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.
Background:
Glioma is an aggressive type of brain tumor that originated from neuroglia cells, accounts for about 80% of all malignant brain tumors. Glioma aggressiveness has been associated with extreme cell proliferation, invasion of malignant cells, and resistance to chemotherapies. Due to resistance to common therapies, glioma affected patients' survival has not been remarkably improved. ZEB2 (SIP1) is a critical transcriptional regulator with various functions during embryonic development and wound healing that has abnormal expression in different malignancies, including brain tumors. ZEB2 overexpression in brain tumors is attributed to an unfavorable state of the malignancy. Therefore, we aimed to investigate some functions of ZEB2 in two different glioblastoma U87 and U373 cell lines.
Methods:
In this study, we investigated the effect of ZEB2 knocking down on the apoptosis, cell cycle, cytotoxicity, scratch test of the two malignant brain tumor cell lines U87 and U373. Besides, we investigated possible proteins and microRNA, SMAD2, SMAD5, and miR-214, which interact with ZEB2 via in situ analysis. Then we evaluated candidate gene expression after ZEB2-specific knocking down.
Results:
We found that ZEB2 suppression induced apoptosis in U87 and U373 cell lines. Besides, it had cytotoxic effects on both cell lines and reduced cell migration. Cell cycle analysis showed cell cycle arrest in G0/G1 and apoptosis induction in U87 and U373 cell lines receptively. Also, we have found that SAMAD2/5 expression was reduced after ZEB2-siRNA transfection and miR-214 upregulated after transfection.
Conclusions:
In line with previous investigations, our results indicated a critical oncogenic role for ZEB2 overexpression in brain glioma tumors. These properties make ZEB2 an essential molecule for further studies in the treatment of glioma cancer.
Insights
Suppressing ZEB2 in glioblastoma cells induced apoptosis and reduced cell migration, indicating its oncogenic role. These findings highlight ZEB2 as a potential therapeutic target for brain tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is an aggressive brain tumor characterized by rapid cell proliferation and treatment resistance.
- ZEB2 (SIP1) is a transcriptional regulator overexpressed in malignancies, correlating with poor prognosis.
- Investigating ZEB2's function is crucial for understanding glioma progression and developing new therapies.
Purpose of the Study:
- To investigate the functional role of ZEB2 in glioblastoma U87 and U373 cell lines.
- To determine the effects of ZEB2 suppression on apoptosis, cell cycle, and migration.
- To explore the interaction of ZEB2 with SMAD2, SMAD5, and miR-214.
Main Methods:
- Utilized ZEB2-specific siRNA to knock down gene expression in U87 and U373 glioblastoma cells.
- Assessed apoptosis, cell cycle progression, cytotoxicity, and cell migration (scratch test).
- Performed in situ analysis to investigate interactions with SMAD2, SMAD5, and miR-214, followed by candidate gene expression evaluation.
Main Results:
- ZEB2 suppression induced apoptosis and exhibited cytotoxic effects in both cell lines.
- Reduced cell migration was observed upon ZEB2 knockdown.
- Cell cycle analysis revealed G0/G1 arrest and apoptosis induction; SMAD2/5 expression decreased, while miR-214 expression increased post-transfection.
Conclusions:
- ZEB2 overexpression plays a critical oncogenic role in brain glioma tumors.
- ZEB2 is a significant molecule for further research into glioma cancer treatment strategies.
- Targeting ZEB2 may offer a promising therapeutic avenue for glioma patients.
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