title: miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2.
abstract: Glioblastoma development is often associated with alteration in the activity and expression of cell cycle regulators, such as cyclin-dependent kinases (CKDs) and cyclins, resulting in aberrant cell proliferation. Recent studies have highlighted the pivotal roles of miRNAs in controlling the development and growth of glioblastoma. Here, we provide evidence for a function of miR-340 in the inhibition of glioblastoma cell proliferation. We found that miR-340 is downregulated in human glioblastoma tissue samples and several established glioblastoma cell lines. Proliferation and neurosphere formation assays revealed that miR-340 plays an oncosuppressive role in glioblastoma, and that its ectopic expression causes significant defect in glioblastoma cell growth. Further, using bioinformatics, luciferase assay and western blot, we found that miR-340 specifically targets the 3'UTRs of CDK6, cyclin-D1 and cyclin-D2, leading to the arrest of glioblastoma cells in the G0/G1 cell cycle phase. Confirming these results, we found that re-introducing CDK6, cyclin-D1 or cyclin-D2 expression partially, but significantly, rescues cells from the suppression of cell proliferation and cell cycle arrest mediated by miR-340. Collectively, our results demonstrate that miR-340 plays a tumor-suppressive role in glioblastoma and may be useful as a diagnostic biomarker and/or a therapeutic avenue for glioblastoma.
authors.affiliation: Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001, China.
authors.forename: Xuhai
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Neurology, Daqing Longnan Hospital, Daqing, Heilongjiang, 163001 China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin City, Harbin, Heilongjiang 150026, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Jiahang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China. Electronic address: guomian_hyd@163.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Guo
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics*; D056742:Cyclin D2 / Q000235:genetics*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics*; D017931:DNA Primers; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D056742:Cyclin D2; D017931:DNA Primers; C570046:MIRN340 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
keywords: CDK; Cell cycle; Cyclin; Glioblastoma; miR-340