Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells |
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Authors: | Ren Feng Lei Dong |
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Institution: | 1.Department of Medical Administration, Tianjin Huanhu Hospital, Tianjin 300060, China;2.Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA 30322, USA |
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Abstract: | The aim of this study was to investigate signaling pathways for reversal of microRNA-127-mediated multi-drug resistance (MDR) in gliomas cells. Adriamycin-resistant glioma cell lines U251/adr and U87-MG/adr were established and we found that anti-microRNA-127 markedly reduced microRNA-127 expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased apoptosis and the content of intracellular Rh123. Silencing of microRNA-127 significantly increased the sensitivity of U251/ADR and U87-MG/adr cells to adriamycin, compared to cells transfected with negative control siRNA. Silencing of microRNA-127 also significantly reduced the mRNA and protein expression levels of MDR1 and MRP1, which are major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. And Runx2, p53, bcl-2 and survivin, which are important role in cell apoptosis, also markedly changed after microRNA-127 silencing. In addition, down-regulating microRNA-127 decreased the level of phosphorylated-Akt. Our data indicate that down-regulation of micorRNA-127 can trigger apoptosis and overcome drug resistance of gliomas cells. Therefore, this resistance of adriamycin in gliomas can be cancelled by silencing expression of microRNA-127. |
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Keywords: | microRNA-127 gliomas adriamycin drug resistance reversal |
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