Correlation between computational insights into non-coding RNA regulatory networks and glioblastoma survival.

Abstract

e14028 Background: Glioblastoma (GBM) is a highly aggressive primary brain tumor with poor prognosis and limited therapeutic options. Emerging evidence highlights the importance of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), in GBM progression. This study aimed to identify key regulatory ncRNAs and their downstream targets to reveal novel biomarkers and potential therapeutic approaches. Methods: We systematically retrieved differentially expressed lncRNAs from 4 databases, LncRNADisease, Cancer LncRNA Census, Lnc2Cancer, and DeepBase, focusing on lncRNAs with documented biological links to GBM and patient survival. Candidate miRNAs associated with these lncRNAs were identified using the Encyclopedia of RNA Interactomes (ENCORI) and subsequently cross-checked against GBM-associated miRNAs from the Database of Differentially Expressed miRNAs in Human Cancers (dbDEMC). Target genes of these miRNAs were gathered from the MicroRNA Data Integration Portal (miRDIP), then matched to survival-linked genes in the Human Protein Atlas. Enrichment analysis via Enrichr-KG elucidated the functional pathways of these targets. Finally, ChIPBase was used to identify transcription factors (TFs) influencing the candidate ncRNAs. Results: In our analysis, HOTAIR was identified as a key upregulated lncRNA in GBM, associated with poor patient survival in all databases. Thirteen miRNAs interacting with HOTAIR were found, three of which (hsa-miR-519a, hsa-miR-519d, and hsa-miR-93) were GBM-specific and downregulated. Seven target genes of these miRNAs, including ANKH, FNDC3B, and EIF4H, were upregulated and correlated with poor prognosis. Enrichment analysis revealed several critical pathways, including endothelial cell morphogenesis, anion transport regulation, and glycosaminoglycan degradation, all vital to GBM progression and resistance. Conclusions: Our integrative multi-database methodology reveals critical ncRNA interactions, providing a robust framework to unravel tumor-associated regulatory networks. HOTAIR emerges as a central regulator, influencing key miRNAs and survival-linked gene targets in GBM. By identifying pathways like endothelial morphogenesis, glycosaminoglycan metabolism, and translation initiation, this approach highlights promising therapeutic entry points. This bioinformatics-driven strategy underscores HOTAIR’s role in GBM pathogenesis and offers a scalable model for biomarker discovery and precision therapy development in oncology.