Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells.
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.
Department of Medical Administration, Tianjin Huanhu Hospital Tianjin 300060, China.
Ren
R
Feng
Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine Atlanta, GA 30322, USA.
Lei
L
Dong
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D000903:Antibiotics, Antineoplastic; D050659:Core Binding Factor Alpha 1 Subunit; D004317:Doxorubicin; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C513055:ABCB1 protein, human; C000595707:BCL2 protein, human; C107489:BIRC5 protein, human; C547276:MIRN127 microRNA, human; C493709:RUNX2 protein, human; C495901:TP53 protein, human; C421109:multidrug resistance-associated protein 1
adriamycin; drug resistance reversal; gliomas; microRNA-127