title: miR-101 acts as a tumor suppressor by targeting Kruppel-like factor 6 in glioblastoma stem cells.
abstract: OBJECTIVE
  Great interest persists in useful therapeutic targets in glioblastoma (GBM). Deregulation of microRNAs (miRNAs) expression has been associated with cancer formation through alterations in gene targets. In this study, we reported the role of miR-101 in human glioblastoma stem cells (GSCs) and the potential mechanisms.
  
  
  RESULTS
  Quantitative real-time PCR showed that miR-101 expression was decreased in GSCs. Overexpression of miR-101 reduced the proliferation, migration, invasion, and promoted apoptosis of GSCs. One direct target of miR-101, the transcription factor Kruppel-like factor 6 (KLF6), was identified using the Dual-Luciferase Reporter Assay System, which mediated the tumor suppressor activity of miR-101. This process was coincided with the reduced expression of Chitinase-3-like protein 1 (CHI3L1) whose promoter could be bound with and be promoted by KLF6 demonstrated by luciferase assays and chromatin immunoprecipitation assays. The downregulation of CHI3L1 led to the inactivation of MEK1/2 and PI3K signal pathways. Furthermore, nude mice carrying the tumors of overexpressed miR-101 combined with knockdown of KLF6 produced the smallest tumors and showed the highest survival rate.
  
  
  CONCLUSIONS
  Our findings provided a comprehensive analysis of miR-101 and further defining it as a potential therapeutic candidate for GBM.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Li-Ni
authors.initials: LN
authors.lastname: Zhao
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Li
authors.forename: Tian-Da
authors.initials: TD
authors.lastname: Feng
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D000071451:Chitinase-3-Like Protein 1; D005909:Glioblastoma / Q000503:physiopathology*; D057809:HEK293 Cells; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008818:Mice, Neurologic Mutants; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D037102:Lectins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C482128:MAP2K2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human
keywords: CHI3L1; Glioblastoma stem cells; KLF6; microRNAs; mir-101