microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma

被引:611
作者
Kefas, Benjamin [1 ]
Godlewski, Jakub [2 ]
Comeau, Laurey [1 ]
Li, Yunqing [1 ]
Abounader, Roger [1 ]
Hawkinson, Michael [1 ]
Lee, Jeongwu [3 ]
Fine, Howard [3 ]
Chiocca, E. Antonio [2 ]
Lawler, Sean [2 ]
Purow, Benjamin [1 ]
机构
[1] Univ Virginia Hlth Syst, Div Neurooncol, Dept Neurol, Charlottesville, VA USA
[2] Ohio State Univ, Dardinger Lab Neurooncol & Neurosci, Dept Neurol Surg, Columbus, OH 43210 USA
[3] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1158/0008-5472.CAN-07-6639
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNAs are noncoding RNAs inhibiting expression of numerous target genes, and a few have been shown to act as oncogenes or tumor suppressors. We show that microRNA-7 (miR-7) is a potential tumor suppressor in glioblastoma targeting critical cancer pathways. miR-7 potently suppressed epidermal growth factor receptor expression, and furthermore it independently inhibited the Akt pathway via targeting upstream regulators. miR-7 expression was down-regulated in glioblastoma versus surrounding brain, with a mechanism involving impaired processing. Importantly, transfection with miR-7 decreased viability and invasiveness of primary glioblastoma lines. This study establishes miR-7 as a regulator of major cancer pathways and suggests that it has therapeutic potential for glioblastoma.
引用
收藏
页码:3566 / 3572
页数:7
相关论文
共 19 条
  • [1] Protein kinase c-a-mediated regulation of low-density lipoprotein receptor-related protein and urokinase increases astrocytoma invasion
    Amos, Samson
    Mut, Melike
    diPierro, Charles G.
    Carpenter, Joan E.
    Xiao, Aizhen
    Kohutek, Zachary A.
    Redpath, Gerard T.
    Zhao, Yunge
    Wang, Jiahu
    Shaffrey, Mark E.
    Hussaini, Isa M.
    [J]. CANCER RESEARCH, 2007, 67 (21) : 10241 - 10251
  • [2] MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells
    Chan, JA
    Krichevsky, AM
    Kosik, KS
    [J]. CANCER RESEARCH, 2005, 65 (14) : 6029 - 6033
  • [3] Extensive modulation of a set of microRNAs in primary glioblastoma
    Ciafrè, SA
    Galardi, S
    Mangiola, A
    Ferracin, M
    Liu, CG
    Sabatino, G
    Negrini, M
    Maira, G
    Croce, CM
    Farace, MG
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (04) : 1351 - 1358
  • [4] miR-15 and miR-16 induce apoptosis by targeting BCL2
    Cimmino, A
    Calin, GA
    Fabbri, M
    Iorio, MV
    Ferracin, M
    Shimizu, M
    Wojcik, SE
    Aqeilan, RI
    Zupo, S
    Dono, M
    Rassenti, L
    Alder, H
    Volinia, S
    Liu, CG
    Kipps, TJ
    Negrini, M
    Croce, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) : 13944 - 13949
  • [5] Characterization of microRNA expression levels and their biological correlates in human cancer cell lines
    Gaur, Arti
    Jewell, David A.
    Liang, Yu
    Ridzon, Dana
    Moore, Jason H.
    Chen, Caifu
    Ambros, Victor R.
    Israel, Mark A.
    [J]. CANCER RESEARCH, 2007, 67 (06) : 2456 - 2468
  • [6] Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme
    Giannini, C
    Sarkaria, JN
    Saito, A
    Uhm, JH
    Galanis, E
    Carlson, BL
    Schroeder, MA
    James, CD
    [J]. NEURO-ONCOLOGY, 2005, 7 (02) : 164 - 176
  • [7] A microRNA component of the p53 tumour suppressor network
    He, Lin
    He, Xingyue
    Lim, Lee P.
    De Stanchina, Elisa
    Xuan, Zhenyu
    Liang, Yu
    Xue, Wen
    Zender, Lars
    Magnus, Jill
    Ridzon, Dana
    Jackson, Aimee L.
    Linsley, Peter S.
    Chen, Caifu
    Lowe, Scott W.
    Cleary, Michele A.
    Hannon, Gregory J.
    [J]. NATURE, 2007, 447 (7148) : 1130 - U16
  • [8] Real-time expression profiling of microRNA precursors in human cancer cell lines
    Jiang, JM
    Lee, EJ
    Gusev, Y
    Schmittgen, TD
    [J]. NUCLEIC ACIDS RESEARCH, 2005, 33 (17) : 5394 - 5403
  • [9] Johnson SM, 2005, CELL, V120, P635, DOI 10.1016/j.cell.2005.01.014
  • [10] Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs
    Lai, EC
    Tam, B
    Rubin, GM
    [J]. GENES & DEVELOPMENT, 2005, 19 (09) : 1067 - 1080