Document Type : Research Articles
Authors
1
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2
Stem Cell Technology Research Center, Tehran, Iran.
3
Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
4
Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
5
Department of Laboratory Sciences, School of Allied Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
6
Department of Virology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Abstract
GBM (Glioblastoma multiforme) is the most prevalent and lethal primary brain tumor. Gene therapy is one of the promising approaches and involves the delivery of genetic therapeutic molecules for specific antitumour response/activity. miRNAs can regulate the cell biology functions including replication, cell growth, and apoptosis by regulating gene expression. In this study, we found that down-regulation of miR-4731 expression occurred in GBM cells. We further determined that miR-4731 behaved as a tumor suppressor by inhibiting GBM cell proliferation. We further investigated the molecular mechanisms of miR-4731 and EGFR, ERK-1,2 and AKT-1,2 in GBM cell lines U87 and U251. The in vitro ectopic expression of miR-4731 affected cell proliferation, migration, and invasion of U87 and U251 cells. Luciferase reporter assays validated that miR-4731 targeted the 3′-untranslated region (3′-UTR) of EGFR. In conclusions, we identified that miR-4731 plays a tumor suppressor role in GBM cell proliferation and migration by targeting EGFR expression, and miR-4731 may act as a novel biomarker for early diagnosis or therapeutic target of GBM.
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