MiRNA-7 Replacement Effect on Proliferation and Tarceva-Sensitivity in U373-MG Cell Line

Document Type: Research Articles

Authors

1 Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.

2 Department of Molecular Medicine and Biotechnology, Arak University of Medical Sciences, Arak, Iran.

3 Department of Oral Medicine, Dental Research Center, Faculty of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.

4 Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.

5 Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.

Abstract

Background: Deregulation of the EGFR signaling pathway activity has been shown to can be effective in resistance to EGFR-TKIs, such as Tarceva (erlotinib), in glioblastoma cells. In addition, reports have shown that the reduction of miRNA-7 expression levels is associated with an increase in the expression of EGFR. Here, we evaluated the effect of miRNA-7 on EGFR expression and sensitivity of the U373-MG glioblastoma to erlotinib. Methods: The effect of miRNA-7 on EGFR expression was examined using RT-qPCR and western blotting. Trypan blue and MTT assays were performed to explore the effect of treatments on cell growth and survival, respectively. The combination index analysis was used to evaluate the interaction between drugs. Apoptosis was measured by ELISA cell death assay. Results: We showed that miRNA-7 markedly inhibited the expression of EGFR and decreased the growth of glioblastoma cells, relative to blank control and negative control miRNA (p < 0.05). Introduction of miRNA-7 synergistically increased the sensitivity of the U373-MG cells to erlotinib. Results of apoptosis assay demonstrated that miRNA-7 can trigger apoptosis and enhance the erlotinib-mediated apoptosis. Conclusions: Our results show that miRNA-7 plays a critical role in the growth, survival and sensitivity of the U373-MG cells to erlotinib by targeting EGFR. Thus, miRNA-7 replacement therapy can become an effective therapeutic procedure in glioblastoma.

Keywords

Main Subjects