Regulation of IL-8 gene expression in gliomas by microRNA miR-93

• Published in: BMC cancer Vol. 15; no. 1; p. 661
• Main Authors: Fabbri, Enrica, Brognara, Eleonora, Montagner, Giulia, Ghimenton, Claudio, Eccher, Albino, Cantù, Cinzia, Khalil, Susanna, Bezzerri, Valentino, Provezza, Lisa, Bianchi, Nicoletta, Finotti, Alessia, Borgatti, Monica, Moretto, Giuseppe, Chilosi, Marco, Cabrini, Giulio, Gambari, Roberto
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-10-2015; BioMed Central
• Subjects: Analysis; Archives & records; Base Sequence; Binding Sites; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Cell cycle; Cell Line, Tumor; Chemokines; Cluster Analysis; Cytokines; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic research; Genetic transcription; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Health aspects; Humans; In Situ Hybridization; Interleukin-8 - chemistry; Interleukin-8 - genetics; Interleukin-8 - metabolism; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; Models, Biological; Neoplasm Grading; Nucleic Acid Conformation; RNA Interference; RNA, Messenger - chemistry; RNA, Messenger - genetics; Transfection; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; United States > US; Italy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-015-1659-1

Different 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.
Here 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.
IL-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).
In 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.