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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

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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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the National Institute for Medical Research Development (NIMAD) for the financial support of this work (Grant No. 942974). The authors would also like to acknowledge Dr. Fatemeh Jamshidi Adegani for her mentorship role in this project and Dr. Marie Shamseddin for native English review.

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Authors and Affiliations

  1. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran

    Fatemeh Gheidari, Mahboubeh Kabiri & Ehsan Seyedjafari

  2. Stem Cell Technology Research Center, Tehran, Iran

    Fatemeh Gheidari

  3. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran

    Ehsan Arefian & Fatemeh Saadatpour

  4. Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Ehsan Arefian

  5. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Ladan Teimoori-Toolabi

  6. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Masoud Soleimani

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  1. Fatemeh Gheidari
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Contributions

The study was conceptualized by EA and MS. The methodology was given by EA, FG, and FS. Formal analysis and investigation were done by FG and EA. Writing and original draft preparation was done by FG and EA. Writing, review, and editing were done by ES, MK and LTT. Funding acquisition was provided by MS and EA. FG and FS performed experiments.

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Correspondence to Ehsan Arefian or Masoud Soleimani.

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Gheidari, F., Arefian, E., Saadatpour, F. et al. 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. Mol Biol Rep 49, 11855–11866 (2022). https://doi.org/10.1007/s11033-022-07903-2

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