MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression

Abstract

Background Pediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool. Methods We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres. Results These microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant (p < 0.001) prognostic performance for miR-1248 was reported with an area under the curve (AUC) of 1.00. We also highlighted a critical oncogenic role for miR-1248 in gliomas tumours. Indeed, high miR-1248 levels maintain low its validated target genes (CDKN1A (p21)/FRK/SPOP/VHL/MTAP) and consequently sustain the activation of oncogenic pathways. Conclusions Altogether, we provide a novel molecular biomarker able to successfully identify pLGG patients associated with disease progression that could support the clinicians in the decision-making strategy, advancing personalized medicine.

Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1

“…It is noteworthy, that impaired mitophagy was previously found in erythroid precursors in MDS patients, which might be associated with early apoptosis and ineffective erythropoiesis [47]. Important role for miR-1248 has repeatedly been described in several types of tumours, affecting cancer cell viability, proliferation, invasion and migration [48][49][50][51][52]. Although precise role of miR-1248 in SF3B1-mutated MDS still remains to be elucidated, our data suggest that regulatory axis SF3B1mut/ZEB1-circRNAs/miR-1248 may at least partly contribute to specific phenotype of this subtype of MDS.…”

Nanoparticles for Drug and Gene Delivery in Pediatric Brain Tumors’ Cancer Stem Cells: Current Knowledge and Future Perspectives

“…Among non-coding RNAs, microRNAs (miRNAs) have been identified as differentially expressed in pediatric brain tumors compared to normal/healthy brains, influencing survival and response to therapy. MiRNA signatures in pediatric brain tumors reveal how miRNA are differentially expressed in tumor with respect to normal tissue [ 95 ], in responders versus non responders to chemotherapy [ 96 ] and even the tumor anatomical location [ 97 ], indicating that some miRNA might be silenced.…”