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The Mir-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-Cycle Arrest and Apoptosis Via Modulating Several Target Genes Of Erbb Signaling Pathway Publisher Pubmed



Gheidari F1, 2 ; Arefian E3, 4 ; Saadatpour F3 ; Kabiri M1 ; Seyedjafari E1 ; Teimooritoolabi L5 ; Soleimani M6
Authors
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Authors Affiliations
  1. 1. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
  2. 2. Stem Cell Technology Research Center, Tehran, Iran
  3. 3. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
  4. 4. Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: Molecular Biology Reports Published:2022


Abstract

Background: Glioblastoma multiforme (GBM) is an aggressive and lethal brain cancer, which is incurable with standard cancer treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in GBM and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in GBM patients, which is responsible for augmented cell proliferation and migration in GBM. Methods and results: Here, miR-429 was overexpressed using lentiviral vectors in U-251 and U-87 GBM cells and it was observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased, as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest and apoptosis in flow cytometry. Conclusions: Altogether, miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for GBM. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.
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