Abstract
BackgroundDifferent strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF). The chemokine Interleukin-8 (IL-8) has been shown to possess both tumorigenic and proangiogenic properties. Although different pathways of induction of IL-8 gene expression have been already elucidated, few data are available on its post-transcriptional regulation in gliomas.MethodsHere we investigated the role of the microRNA miR-93 on the expression levels of IL-8 and other pro-inflammatory genes by RT-qPCR and Bio-Plex analysis. We used different disease model systems, including clinical samples from glioma patients and two glioma cell lines, U251 and T98G.ResultsIL-8 and VEGF transcripts are highly expressed in low and high grade gliomas in respect to reference healthy brain; miR-93 expression is also increased and inversely correlated with transcription of IL-8 and VEGF genes. Computational analysis showed the presence of miR-93 consensus sequences in the 3′UTR region of both VEGF and IL-8 mRNAs, predicting possible interaction with miR-93 and suggesting a potential regulatory role of this microRNA. In vitro transfection with pre-miR-93 and antagomiR-93 inversely modulated VEGF and IL-8 gene expression and protein release when the glioma cell line U251 was considered. Similar data were obtained on IL-8 gene regulation in the other glioma cell line analyzed, T98G. The effect of pre-miR-93 and antagomiR-93 in U251 cells has been extended to the secretion of a panel of cytokines, chemokines and growth factors, which consolidated the concept of a role of miR-93 in IL-8 and VEGF gene expression and evidenced a potential regulatory role also for MCP-1 and PDGF (also involved in angiogenesis).ConclusionIn conclusion, our results suggest an increasing role of miR-93 in regulating the level of expression of several genes involved in the angiogenesis of gliomas.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1659-1) contains supplementary material, which is available to authorized users.
Highlights
Different strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF)
The aim of this research was first to study the expression of microRNA miR-93 and IL-8 gene in low-grade (LGG) and high-grade gliomas (HGG) specimens ex vivo (a), glioma cell lines transfected with antagomiR-93 (b) and pre-miR-93 (c)
The IL-8 and VEGF staining was found mainly associated with the areas showing hypoxic features and most frequently in those astrocytic spindle cells characterizing the “pseudopalizading” pattern, observed in the areas in proximity to hypoxia and hypoxic necrosis, which represents a histological hallmark of the glioblastoma
Summary
Different strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF). Several possible targets of therapeutic interventions against gliomas have been recently proposed, such as EGFR [1], VEGF [2], the Akt-pathway [3] and the NF-kappaB pathway [4]. In addition to these important targets, the production of cytokines and chemokines. Among these proteins, interleukin-8 (IL-8, or CXCL8) is known to be a major promoter of angiogenesis and invasiveness of human gliomas, where it is expressed and secreted at high levels [11,12,13]. Considering that a single miR can recognize several mRNAs and a single mRNA might contains in its sequence (3′UTR, CDS, 5′UTR) several signals for molecular recognition by miRs, it is calculated that more than 60 % of mammalian mRNAs are target of microRNAs [28], controlling metabolic pathways in differentiation, cell cycle and apoptosis [27, 28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
