MicroRNAs miR-16 and miR-519 control meningioma cell proliferation via overlapping transcriptomic programs shared with the RNA-binding protein HuR

Abstract

IntroductionMeningiomas are the most common type of primary central nervous system tumors. In about 80% cases, these tumors are benign and grow very slowly, but the remainder 20% can unlock higher proliferation rates and become malignant. In this study we examined two miRs, miR-16 and miR-519, and evaluated their role in tumorigenesis and cell growth in human meningioma.MethodsA cohort of 60 intracranial grade 1 and grade 2 human meningioma plus 20 healthy meningeal tissues was used to quantify miR-16 and miR-519 expressions. Cell growth and dose-response assays were performed in two human meningioma cell lines, Ben-Men-1 (benign) and IOMM-Lee (aggressive). Transcriptomes of IOMM-lee cells were measured after both miR-mimics transfection, followed by integrative bioinformatics to expand on available data. ResultsIn tumoral tissues, we detected decreased levels of miR-16 and miR-519 when compared with arachnoid cells of healthy patients (miR-16: P=8.7e-04; miR-519: P=3.5e-07). When individually overexpressing these miRs in Ben-Men-1 and IOMM-Lee, we observed that each showed reduced growth (P<0.001). In IOMM-Lee cell transcriptomes, downregulated genes, among which ELAVL1/HuR (miR-16: P=6.1e-06; miR-519:P=9.38e-03), were linked to biological processes such as mitotic cell cycle regulation, pre-replicative complex, and brain development (FDR<1e-05). Additionally, we uncovered a specific transcriptomic signature of miR-16/miR-519-dysregulated genes which was highly enriched in HuR targets (>6-fold; 79.6% of target genes). DiscussionThese results were confirmed on several public transcriptomic and microRNA datasets of human meningiomas, hinting that the putative tumor suppressor effect of these miRs is mediated, at least in part, via HuR direct or indirect inhibition.

MicroRNAs in meningiomas: Potential biomarkers and therapeutic targets

“…The identified transcriptomic signature strengthens the association between these miRNAs and HuR targets, hinting at their critical role in modulating biological processes associated with meningioma pathogenesis. The robustness of the study was further confirmed by screening publicly available transcriptome and miRNA datasets from human meningiomas, highlighting the potential clinical relevance of miR-16–5p and hsa-miR-519a-5p as therapeutic targets for meningioma treatment [ 59 ]. Fig.…”

“…Hergalant et al found that tumor tissues showed decreased levels of miR-16–5p and hsa-miR-519a-5p compared to arachnoid cells from healthy patients [ 59 ]. Individual overexpression of these miRs in Ben-Men-1 and IOMM-Lee resulted in decreased cell growth.…”