title: MicroRNA-98 Attenuates Cell Migration and Invasion in Glioma by Directly Targeting Pre-B Cell Leukemia Homeobox 3.
abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The extraordinary invasion of human GBM into adjacent normal brain tissues contributes to treatment failure. However, the mechanisms that control this process remain poorly understood. Increasing evidence has demonstrated that microRNAs are strongly implicated in the migration and invasion of GBM. In this study, we found that microRNA-98 (miR-98) was markedly downregulated in human glioma tissues and cell lines. Functional experiments indicated that restored expression of miR-98 attenuated glioma cell invasion and migration, whereas depletion of miR-98 promoted glioma cell invasion and migration. Subsequent investigation showed that pre-B-cell leukemia homeobox 3 (PBX3), an important transcription factor that controls tumor invasion, was a direct and functional target of miR-98 in GBM cells. Consistently, an orthotopic mouse model also demonstrated the suppressive effects of miR-98 overexpression on tumor invasion and PBX3 expression. Silencing of PBX3 using small interfering RNA inhibited the migratory and invasive capacities of glioma cells, whereas reintroduction of PBX3 into glioma cells reversed the anti-invasive function of miR-98. Furthermore, depletion of PBX3 phenocopied the effects of miR-98 overexpression in vivo. Finally, quantitative real-time polymerase chain reaction results showed that miR-98 was negatively correlated with PBX3 expression in 24 glioma tissues. Thus, we propose that PBX3 modulation by miR-98 has an important role in regulating GBM invasion and may serve as therapeutic target for GBM.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. jijing@njmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. neurosurgery1958@163.com.
authors.forename: Ning
authors.identifier: http://orcid.org/0000-0001-5206-6501
authors.initials: N
authors.lastname: Liu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting / Q000379:methods*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C090466:proto-oncogene protein Pbx3
keywords: Glioma; Invasion; Migration; PBX3; miR-98