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Cell Journal، جلد ۱۶، شماره Suppl ۱، صفحات ۱۶۴-۱۶۴
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عنوان انگلیسی Ps-133: A Novel Predicted Target for miR-126 Involved in Neurotrophin Signaling Pathway and Cancer Stem Cell Formation in Glioma
چکیده انگلیسی مقاله Objective: Gliomas compose of ~30% of all brain and central nervous system tumors and 80% of all malignant brain tumors. MicroRNAs (miRNAs) are small, single-stranded RNAs with an important role in the regulation of gene expression. miR-126 is found on chromosome 9 within intron 7 of the EGFL7 gene. IRS1 was significantly inhibited by upregulation of miR-126. IRS1 is capable to affect PI3K/Akt pathway through neurotrophin pathway. Neurotrophin pathway plays a significant role in neural cell differentiation. While KRAS gene implicated in the role of cellular differentiation affects PI3K/Akt pathway. Also, Ras and PI3K proteins involving the formation pathways of glioma cancer stem cells include Notch, Hedgehog (Hh), Wnt/ beta-catenin and focal adhesion pathways. It is anticipated that upregulated miR-126 via downregulation of IRS1 caused glioma cancer stem cell. Here, we used molecular signaling pathway enrichment analysis approach to determine possible mechanism of association of miR-126 and IRS1 within neurotrophin pathway. Materials and Methods: Validated and predicted targets (targetome) of miR-126 were collected of miRtarbase and miRwalk databases, respectively. Then, approximate expression of miR-126 targetome in glioma tissue was examined using Unigene database. Finally, in silico molecular pathway enrichment analysis was carried out by DAVID database to explore which of signaling pathway is related to miR-126 targetome and how miR-126 functions in the formation of glioma. Results: Our data determined that some KEGG pathways including neurotrophin and focal adhesion signaling pathways are the most statistically associated with miR-126 targetome. Interestingly, four genes including KRAS, PIK3R2, IRS1 and CRK were influenced by miR-126. Among them, PIK3R2 and KRAS have the most effective role in focal adhesion and neurotrophin pathways. Conclusion: According to our data, overexpression of miR-126 may lead to downregulation of IRS1 in the formation of glioma cancer stem cells.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/458
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