Abstract
Meningioma is the most common primary intracranial brain tumour, classified as benign (WHO I, 70%), atypical (WHO II, 30%) and anaplastic/malignant (WHO III, 1–3%). The 3-year recurrence rate for WHO I tumours is 40% and it is much higher in WHO II-III1. To date, meningioma classification is based only on histopathological characterization, and no circulating biomarkers have been identified to predict tumour progression2. Indeed, microRNAs are promising circulating biomarkers because they can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies3. Previously, Cyclin D1 overexpression was suggested as a possible meningioma biomarker as it correlates with proliferative activity and tumour grade, while high levels of Cyclin E1 were shown to correlate with higher recurrence rates4,5. In this study, we showed, for the first time, that the transcription factor GATA-4 is overexpressed in malignant meningioma cells and tissues, controlling the miR-15 family (miR-15a/b-16-497-195) expression. Moreover, we proved that the miR-497~195 cluster not only regulates Cyclin D1-D2-D3 and E1 levels, but it also modulates GATA-4 expression in meningioma. Moreover, we showed that the levels of miR-497~195 cluster are significantly lower in exosomes derived from higher grade meningioma patients’ blood serum, supporting their potential as diagnostic biomarkers.