title: miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways.
abstract: Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3'-untranslated region (3'-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.
authors.affiliation: Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Huang
authors.affiliation: The Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
authors.forename: Simiao
authors.initials: S
authors.lastname: Yu
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, P.R. China.
authors.forename: Shizhu
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; C549242:MIRN7-1 microRNA, human; C512478:EGFR protein, human