MiR-16 and miR-519 suppress tumor cell proliferation in meningiomas via HuR inhibition

We investigated the relative expression levels of these miRs in a series of meningioma and normal meningeal tissues. The effects of miR-16 and miR-519 on cell growth and transcriptome were assessed in vitro using two human cell lines (Ben-Men-1 and IOMM-Lee). Both miR-16 and miR-519 were significantly downregulated in meningioma compared with normal meningeal tissue. Overexpression of either miR in IOMM-Lee and Ben-Men-1 cells significantly reduced cell growth. The transfection of miR-16 and miR-519 significantly downregulated HuR mRNA, and genes involved in various functions such as pre-replicative complex, mitotic recombination, S phase and M phase of cell cycle, and upregulated genes implicated in cell junction, and positive regulation of cell death. Cell-cycle-related genes associated cluster included HuR mRNA (ELAVL1), and was highly enriched with HuR gene targets. IOMM-Lee cells transfected with either miR Mimic hsa-miR-16-5p (miR16 ; n=6 ; biological replicates), miR Mimic hsa-miR-519a-3p (miR519 ; n=6 ; biological replicates) and mirVana miR Mimic Negative Control (ctrl ; n=6 ; biological replicates).

本研究针对一系列脑膜瘤与正常脑膜组织中各类微小RNA（miR）的相对表达水平展开探究。本研究采用两种人类细胞系（Ben-Men-1与IOMM-Lee），在体外环境中评估了miR-16与miR-519对细胞生长及转录组的影响。结果显示，相较于正常脑膜组织，脑膜瘤组织中miR-16与miR-519均呈现显著下调表达。在IOMM-Lee与Ben-Men-1细胞中过表达任意一种miR，均可显著抑制细胞生长。转染miR-16与miR-519可显著下调HuR mRNA，同时下调参与复制前复合物、有丝分裂重组、细胞周期S期与M期等多种生物学过程的基因，并上调与细胞连接、细胞死亡正调控相关的基因。与细胞周期相关的基因聚类模块包含HuR mRNA（ELAVL1），且该模块显著富集于HuR基因的靶标集合中。本次实验中，转染以下试剂的IOMM-Lee细胞分组为：miR模拟物hsa-miR-16-5p（记为miR16，n=6，生物学重复）、miR模拟物hsa-miR-519a-3p（记为miR519，n=6，生物学重复）以及mirVana miR模拟物阴性对照（记为ctrl，n=6，生物学重复）。