title: Co-inhibition of microRNA-10b and microRNA-21 exerts synergistic inhibition             on the proliferation and invasion of human glioma cells.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene             regulators. Alterations in the expression of miRNAs have been implicated in the             pathogenesis and development of most human malignancies. Recent data indicate             that microRNA-21 and microRNA-10b are significantly elevated in glioblastoma multiforme             (GBM) suggesting their role in the regulation of multiple genes associated with             cancer. In this study, U87MG human glioblastoma cells were treated with miRNA             inhibitors targeting miR-10b and miR-21, alone or in combination. The results             showed that the miR-21 inhibitor additively interacted with miR-10b inhibitor             on U87MG cells. The 50% inhibitory concentration values were dramatically decreased             in cells treated with the combination of miR-10b and miR-21 inhibitors. Furthermore,             inhibitors synergistically combined, enhanced apoptosis significantly and reduced             invasion ability assessed by flow cytometry and Transwell migration assay. Thus,             the miR-21 inhibitor may interrupt the activity of EGFR pathways, increasing PDCD4             and TPM1 expression and reducing MMP activities, independently of PTEN status.             Meanwhile, miR-10b inhibitor reduced by Twist proceeds to inhibit translation             of the mRNA encoding HOXD10 leading to the increase of the expression of the well-characterized             pro-metastatic gene RHOC. Taken together, these data strongly suggest that a combination             of miR-21 inhibitor and miR-10b inhibitor could be an effective therapeutic strategy             for controlling the growth of GBM by inhibiting oncogene expression and overexpressing             tumor suppressor genes. Moreover, a regulatory strategy based on the combination             of miRNA inhibitors may provide insights into the mechanisms of the modulation             of signaling genes involved in tumor cell apoptosis and invasiveness.
authors: Department of Pathophysiology, College of Veterinary Medicine,                     China Agricultural University, Beijing 100094, P.R. China.
authors: Chang G
authors: CG
authors: Dong
authors: William K K
authors: WK
authors: Wu
authors: Su Y
authors: SY
authors: Feng
authors: Xiao J
authors: XJ
authors: Wang
authors: Jun F
authors: JF
authors: Shao
authors: Jian
authors: J
authors: Qiao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014335:Tropomyosin / Q000096:biosynthesis / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D018398:Homeodomain Proteins; C547183:MIRN10 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C490775:TPM1 protein, human; D014157:Transcription Factors; D014335:Tropomyosin; C072064:HOXD10 protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020782:Matrix Metalloproteinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein