title: Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo.
abstract: MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate genes expression by binding to the 3' untranslated region (UTR) of targets mRNAs and play critical roles in cancer pathways. Malignant glioma is the most common and highly lethal central nervous system tumor for which little effective treatment is available over several decades. The purpose of this study was to explore the therapeutic potential of plasmid-based microRNA-7 (miR-7) for gliomas in vivo. Enhancing miR-7 levels in vitro could significantly induce cell apoptosis, and inhibit cell proliferation, cell migration and invasion. Western blotting analysis was performed, which indicated that miR-7 directly inhibited epidermal growth factor receptor (EGFR) and further antagonized the downstream protein kinases including ERK, Akt and Stat3. Furthermore, systemic administration of miR-7 encapsulated in cationic liposome resulted in glioma xenografts growth arrest and the metastatic nodules decrease effectively in a sequence-specific manner. In this study, miR-7 was applied in glioma treatment for the first time in vivo. Our findings suggested that the plasmid-mediated gene therapy with miR-7 appeared to be a promising candidate for the development of new antitumor and anti-metastasis treatment for human glioma.
authors: Sichuan University, Chengdu, People's Republic of China.
authors: W
authors: W
authors: Wang
authors: L X
authors: LX
authors: Dai
authors: S
authors: S
authors: Zhang
authors: Y
authors: Y
authors: Yang
authors: N
authors: N
authors: Yan
authors: P
authors: P
authors: Fan
authors: L
authors: L
authors: Dai
authors: H W
authors: HW
authors: Tian
authors: L
authors: L
authors: Cheng
authors: X M
authors: XM
authors: Zhang
authors: C
authors: C
authors: Li
authors: J F
authors: JF
authors: Zhang
authors: F
authors: F
authors: Xu
authors: G
authors: G
authors: Shi
authors: X L
authors: XL
authors: Chen
authors: T
authors: T
authors: Du
authors: Y M
authors: YM
authors: Li
authors: Y Q
authors: YQ
authors: Wei
authors: H X
authors: HX
authors: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D008081:Liposomes; D035683:MicroRNAs; D012333:RNA, Messenger; C549242:MIRN7-1 microRNA, human