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

Sébastien Hergalant; Jean-Matthieu Casse; Abderrahim Oussalah; Rémi Houlgatte; Déborah Helle; Fabien Rech; Laurent Vallar; Jean-Louis Guéant; Jean-Michel Vignaud; Shyue-Fang Battaglia-Hsu; Guillaume Gauchotte

doi:10.3389/fonc.2023.1158773

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

Front Oncol. 2023 Aug 2:13:1158773. doi: 10.3389/fonc.2023.1158773. eCollection 2023.

Authors

Sébastien Hergalant¹, Jean-Matthieu Casse¹, Abderrahim Oussalah^{1

2

3}, Rémi Houlgatte¹, Déborah Helle¹, Fabien Rech^{4

5}, Laurent Vallar⁶, Jean-Louis Guéant^{1

2

3}, Jean-Michel Vignaud^{1

7

8}, Shyue-Fang Battaglia-Hsu^{2

3

5}, Guillaume Gauchotte^{1

7

8}

Affiliations

¹ INSERM, U1256, NGERE - Nutrition, Genetics, and Environmental Risk Exposure, Faculty of Medicine of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France.
² Department of Molecular Medicine and Personalized Therapeutics, University Hospital of Nancy (CHRU), Vandoeuvre-lès-Nancy, France.
³ Department of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy (CHRU), Vandoeuvre-lès-Nancy, France.
⁴ Department of Neurosurgery, University Hospital of Nancy (CHRU), Nancy, France.
⁵ CNRS, UMR7039, CRAN - Centre de Recherche en Automatique de Nancy, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
⁶ Genomics and Proteomics, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg.
⁷ Department of Biopathology Institut De Cancérologie de Lorraine (CHRU-ICL), University Hospital of Nancy (CHRU), Nancy, France.
⁸ Centre de Ressources Biologiques BB-0033-00035, University Hospital of Nancy (CHRU), Nancy, France.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Discussion: 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.

Keywords: HuR; meningioma; miR-16; miR-519; microRNA; proliferation; transcriptomics; tumorigenesis.

Grants and funding

GIRCI-EST and La Région Lorraine. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.