Identification of a ceRNA Network Regulating Malignant Transformation of Isocitrate Dehydrogenase Mutant Astrocytoma: An Integrated Bioinformatics Study.

Abstract

Introduction: Astrocytoma is the most common glioma, accounting for about 65% of glioblastoma. Its malignant transformation is also one of the important causes of patient mortality, making it the most prevalent and difficult to treat in primary brain tumours. However, little is known about the underlying mechanisms of this transformation.

Methods: In this study, we established a ceRNA network to screen out the potential regulatory pathways involved in the malignant transformation of IDH-mutant astrocytomas. Firstly, the Chinese Glioma Genome Atlas (CGGA) was employed to compare the expression levels of the differential expressed genes (DEGs) in astrocytomas. Then, the ceRNA-regulated network was constructed based on the interaction of lncRNA-miRNA-mRNA. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the main functions of the differentially expressed genes. COX regression analysis and log-rank test were combined to screen the ceRNA network further. In addition, quantitative real-time PCR (qRT-PCR) was conducted to identify the potential regulatory mechanisms of malignant transformation in IDH-mutant astrocytoma. We constructed a ceRNA network with 34 lncRNAs, 29 miRNAs, and 71 mRNAs.

Results: GO and KEGG analyses results suggested that DEGs were associated with tumor-associated molecular functions and pathways. In addition, we screened two ceRNA regulatory networks using Cox regression analysis and log-rank test. QRT-PCR assay identified the NAA11/hsa- miR-142-3p/GS1-39E22.2 regulatory axis of the ceRNA network to be associated with the malignant transformation of IDH-mutant astrocytoma.

Conclusion: The discovery of this mechanism deepens our understanding of the molecular mechanisms of malignant transformation in astrocytomas and provides new perspectives for exploring glioma progression and targeted therapies.