title: MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-β1.
abstract: Cell migration and invasion are key processes involved during tumor metastasis. Recently, microRNAs (miRs) have been demonstrated to play important roles in the regulation of cancer metastasis. However, the underlying mechanisms remain unknown. Here, we aimed to investigate the exact role of miR-663 in the metastasis of glioblastoma as well as the underlying mechanisms. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that miR-663 was significantly downregulated in glioblastoma tissues (n=25), when compared to that in normal brain tissues (n=15). In addition, its expression levels were also reduced in human glioblastoma cell lines, A172 and U87. Furthermore, restoration of miR-663 expression led to a significant decrease in the cell proliferation, migration and invasion of human glioblastoma A172 and U87 cells. We further identified TGF-β1 as a direct target of miR-663, and found that the expression of TGF-β1 was negatively mediated by miR-663 at the post-transcriptional level in glioblastoma cells. Moreover, overexpression of TGF-β1 significantly reversed the inhibitory effects of miR-663 upregulation on the proliferation, migration and invasion in A172 and U87 cells. In addition, our data suggest that MMP2 and E-cadherin, a key factor in epithelial-mesenchymal transition (EMT), are involved in the miR-633/TGF-β1-mediated metastasis of glioblastoma. In summary, miR-663 plays an inhibitory role in the regulation of proliferation, migration and invasion of glioblastoma cells, partly at least, via direct mediation of TGF-β1 as well as downstream MMP2 and E-cadherin. Therefore, we suggest that miR-663 is a potential candidate for the prevention of glioblastoma metastasis.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Qizhuang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Renjun
authors.initials: R
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Jincan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000502:physiology; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D017930:Genes, Reporter; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000502:physiology*; D012334:RNA, Neoplasm / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2