Prognostic miR-1/-26a-1/-487b signature predicts glioma progression via SH3PXD2B/EFHD2 targeting

Abstract Gliomas are aggressive brain tumors that remain challenging to diagnose and treat. Despite standard-of-care therapies, most patients recur, underscoring an unmet need for novel biomarkers to elucidate tumor evolution. MicroRNAs (miRNAs) play crucial roles in glioma biology by modulating tumorigenesis. We previously identified a non-invasive diagnostic/prognostic miRNA signature (miR-1-3p/miR-26a-1-3p/miR-487b-3p) which exerts oncosuppressive functions in glioma cells, prominently effecting the inhibition of invading targeting SH3PXD2A/SH3PXD2B/EFHD2 genes. Here, we investigated the miR-1/-26a-1/-487b- SH3PXD2A/SH3PXD2B/EFHD2 network as a progression indicator using datasets of primary/recurrent gliomas. We found that the three-miRNA signature is upregulated in primary vs. recurrent patients, whereas SH3PXD2A/SH3PXD2B/EFHD2 are downregulated in primary patients. It is worthy to note that, this network correlates with improved survival. These findings were validated by RT-qPCR in tissues of a paired-primary/recurrent cohort ( n = 42). Univariate and multivariate Cox-regression analyses showed that high miR-1-3p/miR-26a-1-3p/miR-487b-3p signature expression independently correlated with prolonged progression-free-survival in this cohort. Additionally, we developed a digital PCR multiplex clinical research assay (G-SMART), for the simultaneous absolute quantification of miR-1-3p/miR-26a-1-3p/miR-487b-3p, which may provide a fast and sensitive tool in the clinical setting. In conclusion, the miR-1-3p/miR-26a-1-3p/miR-487b-3p and its targets are key axes that are progressively dysregulated upon glioma progression. Hence, this regulatory network might offer a prognostic tool for disease monitoring, leading us to hypothesize a translational value of our findings for a more precise and patient-tailored approach.