Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines
| Autor: | Behzad Baradaran, Nima Hemmat, Afshin Derakhshani, Neda Khosravi, Sahar Safaee, Nicola Silvestris, Masoumeh Fardi |
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| Rok vydání: | 2020 |
| Předmět: |
Cell cycle checkpoint
Brain tumor Pharmaceutical Science Biology Article Analytical Chemistry lcsh:QD241-441 03 medical and health sciences 0302 clinical medicine lcsh:Organic chemistry Glioma Drug Discovery microRNA medicine Biomarkers Tumor Tumor Cells Cultured Humans Physical and Theoretical Chemistry U87 RNA Small Interfering 030304 developmental biology Cell Proliferation Zinc Finger E-box Binding Homeobox 2 ZEB2 0303 health sciences Cell growth Brain Neoplasms Organic Chemistry Cell Cycle glioblastoma apoptosis Cell migration Cell cycle medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Chemistry (miscellaneous) 030220 oncology & carcinogenesis siRNA Cancer research TGF-β pathway Molecular Medicine |
| Zdroj: | Molecules Volume 26 Issue 4 Molecules, Vol 26, Iss 901, p 901 (2021) |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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