MicroRNA-564 is downregulated in glioblastoma and inhibited proliferation and invasion of glioblastoma cells by targeting TGF-β1.
Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-β1 (TGF-β1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-β. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-β-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-β1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.
Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China.
Chunming
C
Jiang
Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
Fang
F
Shen
Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China.
Jianmin
J
Du
Translational Medicine Office of Hangzhou Cancer Institute, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China.
Zhaoyang
Z
Hu
Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China.
Xiaoli
X
Li
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Jin
J
Su
Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Xiaohua
X
Wang
Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China.
Xianmei
X
Huang
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
C577008:MIRN564 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C512478:EGFR protein, human; D066246:ErbB Receptors; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
TGF-β; glioblastoma; microRNA-564; proliferation