title: MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-κB1/MMP9 signaling pathway.
abstract: Recent studies have identified a class of small non-coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA-16 (miR-16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR-16 in gliomagenesis are largely unknown. We have shown that the expression of miR-16 in human brain glioma tissues was lower than in non-cancerous brain tissues, and that the expression of miR-16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR-16 and nuclear factor (NF)-κB1 was negatively correlated with glioma levels. MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR-16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR-16-mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF-κB1/MMP-9 signaling pathway. Therefore, our experiments suggest the possible future use of miR-16 as a therapeutic target in gliomas.
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Yang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Lu
authors.forename: Ting-Feng
authors.initials: TF
authors.lastname: Wu
authors.forename: Da-Dong
authors.initials: DD
authors.lastname: Ding
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Zhao
authors.forename: Gui-Lin
authors.initials: GL
authors.lastname: Chen
authors.forename: Xue-Shun
authors.initials: XS
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Wei
authors.forename: Ling-Chuan
authors.initials: LC
authors.lastname: Guo
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Huang
authors.forename: You-Xin
authors.initials: YX
authors.lastname: Zhou
authors.forename: Zi-Wei
authors.initials: ZW
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: BCL2; Glioma; MMP9; NF-κB1; miR-16