Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling Pathway: A Possible Role in Prevention of Glioma Development

Rouigari, Maedeh; Dehbashi, Moein; Ghaedi, Kamran; Pourhossein, Meraj

doi:10.22074/cellj.2018.4901

Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling Pathway: A Possible Role in Prevention of Glioma Development

Document Type : Original Article

Authors

¹ Isfahan Neuroscience Research Center (INRC), Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

² Isfahan Neuroscience Research Center (INRC), Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran;Genetics Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

³ Cell and Molecular Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

⁴ 4Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences Isfahan, Iran;5Department of Food Science and Technology, Food Security Research Center, School of Nutrition and Food Scienc

10.22074/cellj.2018.4901

Abstract

Objective
For the first time, we used molecular signaling pathway enrichment analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin pathway.
Materials and Methods
In this prospective study, validated and predicted targets (targetome) of miR-126 were collected following searching miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases, respectively. Then, approximate expression of miR-126 targeting in Glioma tissue was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In silico molecular pathway enrichment analysis was carried out by DAVID 6.7 database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is related to miR-126 targeting and how miR-126 attributes to glioma development.
Results
MiR-126 exerts a variety of functions in cancer pathogenesis via suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and VEGF. Our bioinformatic studies implementing DAVID database, showed the involvement of miR-126 target genes in several signaling pathways including cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function, focal adhesion production, chemokine synthesis and secretion and regulation of the actin cytoskeleton.
Conclusion
Taken together, we concluded that miR-126 enhances the formation of glioma cancer stem cell probably via down regulation of IRS-1 in neurotrophin signaling pathway.

Keywords