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Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression

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Abstract

In the fight against glioblastoma, circular RNA is emerging as a functional molecule. However, how circular RNA (circRNA) is regulated and what role it plays is still a mystery. In this research, different bioinformatics approaches were used to evaluate glioblastoma circRNA sequencing and array data, with the goal of developing a putative molecular sponge mechanism control network. The circRNAs were obtained from the Gene Expression Omnibus datasets. MicroRNA-circRNA interactions were predicted using CircInteractome. The microRNAs' expression and survival trends were screened using the TCGA database. MicroRNA gene targets were predicted using the MiRnet database. Sponge network gene candidates were screened using data from the GEPIA. The roles of the targeted genes were to be explained by analyzing data from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. To build the network and display the outcomes, we utilized python program, and enrichment online Bioinformatics databases. The circRNAs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circITGA4_003, hsa_circ_0030855, hsa_circ_0030857 were chosen from among GBM patients and control group. Upregulation of hsa-miR-1468, hsa-miR-3683, hsa-miR-1273c, and hsa-miR-4665-3p were associated with a poor prognosis in GBM. MicroRNA targets such as ITGA4, LAMA2, EGFR, PTEN, COL1A4, and NCAM2 were analyzed using expression and survival data. The Apoptosis, cell adhesion molecules, PI3K/AKT and P53 signaling pathways were the most abundant functional categories among gene targets. The circRNA molecular sponge regulatory network includes hsa-miR-1468 and hsa-miR-4665-3p. In this network, hs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circ_0030857, EGFR, PTEN, and ITGA4 may represent GBM therapeutic targets. Their role in GBM needs additional study.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We thank all colleagues in the core facilities for their support.

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sara Tutunchi

  2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Tech Royan Institute for Stem Cell Biology and Technology, Tehran, Iran

    Ahmad Bereimipour

  3. Department of Biological Sciences and BioDiscovery Institute, University of North Texas, Denton, TX, 76203, USA

    Ahmad Bereimipour

  4. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sayyed Mohammad Hossein Ghaderian

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All authors Participated in study design, data collection and evaluation, drafting and statistical analysis. Contributed extensively in interpretation of the data and the conclusion and figure design. All authors performed editing and approving the final version of this paper for submission, also participated in the finalization of the manuscript and approved the final draft.

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Correspondence to Sayyed Mohammad Hossein Ghaderian.

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Tutunchi, S., Bereimipour, A. & Ghaderian, S.M.H. Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression. Mol Biotechnol 66, 90–101 (2024). https://doi.org/10.1007/s12033-023-00735-w

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