title: MiR-154 Functions as a Tumor Suppressor in Glioblastoma by Targeting Wnt5a.
abstract: Recently, deregulated microRNA (miRNA) expression contributes to the development and progression of human glioblastoma. The aim of the present study was to evaluate the level of miR-154 and Wnt5a in glioblastoma tissues and cells. We further investigated the molecular mechanisms of miR-154 and Wnt5a in glioblastoma cell lines. In the present study, we found that miR-154 expression was downregulated in glioblastoma tissues and U87, U251, and A172 cells (all p < 0.001). By contrast, Wnt5a was upregulated. Furthermore, we found that overexpression of miR-154 suppressed cell migration and invasion of U87 and U251 cells. Mechanically, overexpression of miR-154 inhibited epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Importantly, we identified that the 3' untranslated region (3'-UTR) of Wnt5a was a direct target of miR-154. Luciferase reporter assays confirmed that miR-154 binding to the 3'-UTR regions of Wnt5a inhibited the expression of Wnt5a in U87 and U251 cells. At the same time, overexpressed Wnt5a also reversed EMT inhibited by miR-154. In conclusion, this study suggested that high miR-154 expression suppressed glioblastoma cell migration, invasion, and EMT development through targeting Wnt5a, which may be recommended as a therapeutic target for glioblastoma.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Rencong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Dongyang People's Hospital of Zhejiang Province, Dongyang, 322100, Zhejiang, China.
authors.forename: Junkang
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Xituan
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Gangfeng
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Zhen
authors.affiliation: Department of Oncology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, 214002, China. actively0126@126.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. feizhou@fmmu.edu.cn.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000071818:Wnt-5a Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C561122:MIRN154 microRNA, human; D035683:MicroRNAs; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein
keywords: EMT; GBM; MiR-154; Wnt5a