Cytoplasmic overexpression of RNA-binding protein HuR in meningioma is a marker of poor prognosis and specific HuR knockdown decreases meningioma cell growth and resistance to hypoxia

HuR is known to regulate mRNA stability and translatability in cytoplasm. In several human tumors, the level of HuR expression has been shown to correlate with poor disease outcome. In meningioma, however, the prognostic value and the potential pro-oncogenic properties of HuR remain obscure. To clarify these, transcriptome-wide analyses in IOMM-Lee cells were performed to pinpoint the detailed molecular consequences of HuR knockdown. In IOMM-Lee cells, transcriptomic analyses revealed that HuR knockdown deregulated the signaling pathway of HIF1A and upregulated the expression of genes for cytoplasmic mRNA processing body assembly, poly(A)-specific ribonuclease activity, positive regulation of apoptosis, negative regulation of RNA splicing, global genome nucleotide-excision repair, and positive regulation of cell cycle arrest. Interestingly, HuR knockdown under hypoxic culture condition potentiated further the effects of HuR knockdown on cell growth, apoptosis, and HIF1A expression. IOMM-Lee cells transfected with either the Silencer Select Negative Control siRNA#1 (Ctrl ; n=6 ; biological replicates) or Silencer Select siRNA ELAVL1 s4608 (HuR ; n=6 ; biological replicates)