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

Frontiers in Oncology

Oncology

Shyue-Fang Battaglia-Hsu¹  Fabien Rech²  Laurent Vallar³  Jean-Matthieu Casse⁴  Sébastien Hergalant⁴  Rémi Houlgatte⁴  Déborah Helle⁴  Jean-Michel Vignaud⁵  Guillaume Gauchotte⁵  Abderrahim Oussalah⁶  Jean-Louis Guéant⁶ 

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

关键词: miR-16;    miR-519;    microRNA;    HuR;    proliferation;    tumorigenesis;    meningioma;    transcriptomics;   

DOI  :  10.3389/fonc.2023.1158773

 received in 2023-02-04, accepted in 2023-07-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Hergalant, Casse, Oussalah, Houlgatte, Helle, Rech, Vallar, Guéant, Vignaud, Battaglia-Hsu and Gauchotte