Competing endogenous RNA

In molecular biology, competing endogenous RNAs (abbreviated ceRNAs) regulate other RNA transcripts by competing for shared microRNAs (miRNAs).

Models for ceRNA regulation describe how changes in the expression of one or multiple miRNA targets alter the number of unbound miRNAs and lead to observable changes in miRNA activity - i.e., the abundance of other miRNA targets.

Huang et al. identified differentially expressed genes and Competing endogenous RNA (ceRNA) networks in malignant glioma and then constructed Cox/Lasso regression models to further identify the most valuable genes through stepwise refinement. Top-down comprehensive integrated analysis, including functional enrichment, SNV, immune infiltration, transcription factor binding site, and molecular docking analyses, further revealed the regulatory maps among these genes. The results revealed a novel and accurate model (AUC of 0.91 and C-index of 0.84 in the whole malignant gliomas, AUC of 0.90 and C-index of 0.86 in LGG, and AUC of 0.75 and C-index of 0.69 in Glioblastoma) that includes twelve ncRNAs, 1 miRNA, and 6 coding genes. Stepwise logical reasoning based on top-down comprehensive integrated analysis and references revealed crosstalk signaling pathways among these genes that were correlated with the circadian rhythm, tumor immune microenvironment, and cellular senescence pathways. In conclusion, the work reveals a novel model where the newly identified biomarkers may contribute to a precise diagnosis/prognosis and subclassification of malignant glioma, and the identified cross-talk signaling pathways would help to illustrate the noncoding RNA-associated epigenetic regulatory mechanisms of glioma tumorigenesis and aid in targeted therapy ¹⁾.