title: MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein (NOB1).
abstract: Malignant glioma is the most common type of primary brain tumor in adults, characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. Alterations in the activity of the 26S proteasome have been associated with malignant glioma cells, although the specific defects have not been identified. Recently, microRNA-326 (miR-326) was shown to play an important role in glioblastoma and breast cancer, but the underlying molecular mechanisms remain unclear. In the present study, the human Nin one binding protein (NOB1) was identified as a direct target of miR-326 and a potential oncogene in human glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase, delayed cell proliferation and enhanced apoptosis. MiR-326 inhibited colony formation in soft agar and decreased growth of a xenograft tumor model, suggesting that miR-326 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, these processes were shown to involve the MAPK pathway. NOB1 overexpression in human glioma samples was detected by Affymetrix array analysis, and NOB1 mRNA and protein levels were shown to be increased in high-grade glioma compared to low-grade glioma and normal brain tissue. Furthermore, high levels of NOB1 were associated with unfavorable prognosis of glioma patients. Taken together, these results indicate that miR-326 and NOB1 may play an important role in the development of glioma.
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jingxu
authors.initials: J
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.forename: Rong
authors.initials: R
authors.lastname: Qin
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Wang
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
authors.forename: Da
authors.initials: D
authors.lastname: Fu
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C545322:MIRN326 microRNA, human; D035683:MicroRNAs; C506664:NOB1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins