脑膜瘤是最常见的原发性中枢神经系统肿瘤。在大约80%的病例中，这些肿瘤是良性的，生长缓慢，但剩下的20%可以解除较高的增殖速率，并变为恶性。在本研究中，我们检测了两种miRNA，miR-16和miR-519，并评估它们在人脑膜瘤的肿瘤发生和细胞生长中的作用。使用60个颅内1级和2级人类脑膜瘤样本及20个健康的脑膜组织，量化miR-16和miR-519的表达。在两种人脑膜瘤细胞系Ben-Men-1（良性）和IOMM-Lee（侵袭性）中进行了细胞生长和剂量反应实验。在转染miR-mimics后，测量了IOMM-Lee细胞的转录组，并通过综合生物信息学对可用数据进行扩充。在肿瘤组织中，与健康患者的蛛网膜细胞相比（miR-16：P=8.7e-04；miR-519：P=3.5e-07），我们检测到miR-16和miR-519的水平降低。当在Ben-Men-1和IOMM-Lee中分别过度表达这些miRNA时，我们观察到每种miRNA均显示出减少的生长率（P<0.001）。在IOMM-Lee细胞转录组中，与生物学进程如有丝分裂细胞周期调节、前复制复合物和脑发育相关的下调基因（miR-16：P=6.1e-06；miR-519：P=9.38e-03）（FDR<1e-05）。此外，我们发现了miR-16 / miR-519不正常调控的基因的特定转录组特征，在HuR靶基因中富集（>6倍；79.6%的靶基因）。这些结果在多个公共转录组和microRNA数据集的人类脑膜瘤上得到确认，暗示这些miRNA的潜在抑制肿瘤作用至少部分是通过HuR的直接或间接抑制而介导的。版权所有©2023 Hergalant、Casse、Oussalah、Houlgatte、Helle、Rech、Vallar、Guéant、Vignaud、Battaglia-Hsu和Gauchotte。

Meningiomas 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.A 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.In 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).These 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.Copyright © 2023 Hergalant, Casse, Oussalah, Houlgatte, Helle, Rech, Vallar, Guéant, Vignaud, Battaglia-Hsu and Gauchotte.