TY - JOUR
T1 - MicroRNAs miR-16 and miR-519 control meningioma cell proliferation via overlapping transcriptomic programs shared with the RNA-binding protein HuR
AU - Hergalant, Sébastien
AU - Casse, Jean Matthieu
AU - Oussalah, Abderrahim
AU - Houlgatte, Rémi
AU - Helle, Déborah
AU - Rech, Fabien
AU - Vallar, Laurent
AU - Guéant, Jean Louis
AU - Vignaud, Jean Michel
AU - Battaglia-Hsu, Shyue Fang
AU - Gauchotte, Guillaume
N1 - Funding Information:
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.
Publisher Copyright:
Copyright © 2023 Hergalant, Casse, Oussalah, Houlgatte, Helle, Rech, Vallar, Guéant, Vignaud, Battaglia-Hsu and Gauchotte.
PY - 2023/8/2
Y1 - 2023/8/2
N2 - 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.
AB - 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.
KW - HuR
KW - meningioma
KW - microRNA
KW - miR-16
KW - miR-519
KW - proliferation
KW - transcriptomics
KW - tumorigenesis
UR - http://www.scopus.com/inward/record.url?scp=85168260501&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37601663
U2 - 10.3389/fonc.2023.1158773
DO - 10.3389/fonc.2023.1158773
M3 - Article
C2 - 37601663
SN - 2234-943X
VL - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1158773
ER -