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Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression
Sara Tutunchi1, Ahmad Bereimipour2,3, Sayyed Mohammad Hossein Ghaderian4
1Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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.
Insights
Circular RNAs (circRNAs) are key in glioblastoma (GBM). This study identifies specific circRNAs and microRNAs forming a molecular sponge network, revealing potential therapeutic targets like EGFR and PTEN for GBM treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNA (circRNA) is an emerging functional molecule in glioblastoma (GBM) pathogenesis.
- The regulatory mechanisms and precise roles of circRNAs in GBM remain largely uncharacterized.
Purpose of the Study:
- To investigate the regulatory roles of circRNAs in GBM.
- To construct a circRNA-mediated molecular sponge regulatory network.
- To identify potential therapeutic targets for GBM.
Main Methods:
- Bioinformatic analysis of glioblastoma circRNA sequencing and array data from public databases (GEO, TCGA, GEPIA).
- Prediction of microRNA-circRNA interactions using CircInteractome and microRNA gene targets using MiRnet.
- Construction and visualization of the circRNA molecular sponge network using Python and bioinformatics databases.
Main Results:
- Five circRNAs (hsa_circITGA4_002, hsa_circITGA4_001, hsa_circITGA4_003, hsa_circ_0030855, hsa_circ_0030857) were identified in GBM patients.
- Upregulation of specific microRNAs (hsa-miR-1468, hsa-miR-3683, hsa-miR-1273c, hsa-miR-4665-3p) correlated with poor GBM prognosis.
- A molecular sponge network involving hsa-miR-1468 and hsa-miR-4665-3p was constructed, highlighting potential targets like EGFR, PTEN, and ITGA4.
Conclusions:
- The identified circRNAs and microRNAs play significant roles in GBM.
- The constructed circRNA molecular sponge network provides insights into GBM regulation.
- Specific circRNAs and genes (hsa_circITGA4_002, hsa_circITGA4_001, hsa_circ_0030857, EGFR, PTEN, ITGA4) represent promising therapeutic targets for GBM, warranting further investigation.
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