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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Bioinformatics analysis of potential glioblastoma circular RNA sponge network
Liwen Zhao1,2, Pengfei Zhang3, Yang Nan1,4
1Department of Neurosurgery, Tianjin Medical University General Hospital Airport Site, Tianjin, China.
Background:
Circular RNA is emerging functional molecule for glioblastoma. However, the function and regulatory of circular RNA (circRNA) remains unclear. In this study, the circRNA sequencing and array data of glioblastoma were analyzed by multiple bioinformatics methods to establish a potential molecular sponge mechanism regulation network.
Methods:
Gene Expression Omnibus datasets were used to extract circRNAs. CircInteractome was used to predict microRNAs binding to circRNAs. Chinese Glioma Gene Atlas database was used to screen the microRNAs with expression and survival trends. MiRabel database was used to predict potential gene targets of microRNAs. The Cancer Genome Atlas database was used to screen the gene targets of sponge network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were to explain the gene targets functions. R software, Cytoscape software and Bioinformatics website were used to establish the network and visualize the results.
Results:
Hsa_circ_0000219, hsa_circ_0001073 and hsa_circ_0070700 were selected from more than 2000 differentially expressed circRNAs of Gene Expression Omnibus Series (GSE) GSE146463, GSE92322 and GSE86202 datasets. Hsa-miR-1248 and hsa-miR-1290 were up regulated and related to glioblastoma poor prognosis. Targets of these microRNAs including ARHGEF7, CELA2b, RNF11, YPEL1 and ZNF37a were also screened via expression and survival data. Gene targets function were mainly enriched in signal transduction, cell plasma membrane, ATP binding and calcium signaling pathway.
Conclusions:
A circRNA molecular sponge regulatory network including hsa-miR-1248 and hsa-miR-1290 has been established. In this network, hsa_circ_0001073, hsa_circ_0070700, hsa_circ_0000219, hsa-miR-1248, hsa-miR-1290, and RNF11 may have the potential being emerging glioblastoma therapeutic targets. However, their function and significance for glioblastoma need further experiments to verify.
Insights
Circular RNAs (circRNAs) are emerging molecules in glioblastoma research. This study establishes a circRNA-microRNA regulatory network, identifying potential therapeutic targets like hsa_circ_0001073, hsa-miR-1248, and RNF11 for glioblastoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNA (circRNA) is recognized as a significant functional molecule in glioblastoma.
- The precise functions and regulatory mechanisms of circRNAs in glioblastoma remain largely unelucidated.
- This study aims to explore the regulatory roles of circRNAs in glioblastoma through bioinformatics analysis.
Purpose of the Study:
- To establish a molecular sponge regulatory network for circular RNAs in glioblastoma.
- To identify potential therapeutic targets for glioblastoma based on circRNA and microRNA expression patterns.
- To elucidate the functional enrichment of target genes within the identified regulatory network.
Main Methods:
- Utilized Gene Expression Omnibus datasets for circRNA extraction and analysis.
- Employed CircInteractome and miRabel databases for predicting microRNA binding and gene targets.
- Integrated Chinese Glioma Gene Atlas and The Cancer Genome Atlas databases for expression and survival trend analysis.
- Performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for functional annotation.
- Constructed and visualized the regulatory network using R and Cytoscape software.
Main Results:
- Identified three differentially expressed circRNAs (hsa_circ_0000219, hsa_circ_0001073, hsa_circ_0070700) and two microRNAs (hsa-miR-1248, hsa-miR-1290) associated with glioblastoma prognosis.
- Screened potential microRNA targets including ARHGEF7, CELA2b, RNF11, YPEL1, and ZNF37a.
- Functional enrichment analysis revealed significant involvement in signal transduction, cell plasma membrane, ATP binding, and calcium signaling pathways.
Conclusions:
- A circRNA-molecular sponge regulatory network involving hsa-miR-1248 and hsa-miR-1290 was successfully established.
- Specific circRNAs (hsa_circ_0001073, hsa_circ_0070700, hsa_circ_0000219), microRNAs (hsa-miR-1248, hsa-miR-1290), and a target gene (RNF11) show potential as glioblastoma therapeutic targets.
- Further experimental validation is required to confirm the function and significance of these identified molecules in glioblastoma.
