title: MicroRNA-222 promotes tumorigenesis via targeting DKK2 and activating the Wnt/β-catenin signaling pathway.
abstract: MiR-222 in glioma can regulate cell cycle progression and apoptosis. However, the relationship between miR-222 and Wnt/β-catenin signaling pathway in glioma remains unknown. Here, we found that the Dickkopf-2 gene (DKK2) was a direct target of miR-222 by target prediction analysis and dual luciferase reporter assay. RNA interference silencing of DKK2 proved that miR-222 overexpression led to constitutive activation of β-catenin through inhibition of DKK2 expression in glioma cells. Furthermore, miR-222 siRNA significantly inhibited tumorigenesis in vivo. Finally, Western blot analysis showed that miR-222 could regulate the expression of β-catenin and the downstream genes of Wnt/β-catenin signaling pathway. Taken together, our findings reveal a new regulatory mechanism of miR-222 and suggest that miR-222 might be a potential target in glioma therapy.
authors.affiliation: Department of Pediatric Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, PR China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: He
authors.forename: Chenkai
authors.initials: C
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Baocheng
authors.initials: B
authors.lastname: Wang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; C498622:DKK2 protein, human; C525710:MIR222, human