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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Enrica Fabbri, Eleonora Brognara, Giulia Montagner, Claudio Ghimenton, Albino Eccher, Cinzia Cantù, Susanna Khalil, Valentino Bezzerri, Lisa Provezza, Nicoletta Bianchi, Alessia Finotti, Monica Borgatti, Giuseppe Moretto, Marco Chilosi, Giulio Cabrini, Roberto Gambari
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 661 (Oct 08 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 26449498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• MIRN93 microRNA, human
• MicroRNAs
• RNA, Messenger
• Vascular Endothelial Growth Factor A

Topics

• Base Sequence
• Binding Sites
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cluster Analysis
• Gene Expression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, pathology)
• Humans
• In Situ Hybridization
• Interleukin-8 (chemistry, genetics, metabolism)
• MicroRNAs (chemistry, genetics)
• Models, Biological
• Neoplasm Grading
• Nucleic Acid Conformation
• RNA Interference
• RNA, Messenger (chemistry, genetics)
• Transfection
• Vascular Endothelial Growth Factor A (genetics, metabolism)