miR‐101 Acts as a Tumor Suppressor by Targeting Kruppel‐like Factor 6 in Glioblastoma Stem Cells

Summary Background and aims 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 s...

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Published in:CNS neuroscience & therapeutics 2015-01, Vol.21 (1), p.40-51
Main Authors: Yao, Yi‐Long, Ma, Jun, Wang, Ping, Xue, Yi‐Xue, Li, Zhen, Zhao, Li‐Ni, Li, Zhi‐Qing, Feng, Tian‐Da, Liu, Yun‐Hui
Format: Article
Language:English
Subjects:
Adipokines - genetics
Adipokines - metabolism
Animals
Apoptosis - physiology
Cell Movement - physiology
Cell Proliferation - physiology
CHI3L1
Chitinase-3-Like Protein 1
Glioblastoma - physiopathology
Glioblastoma stem cells
HEK293 Cells
Humans
KLF6
Kruppel-Like Factor 6
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Lectins - genetics
Lectins - metabolism
MAP Kinase Kinase 1 - metabolism
MAP Kinase Kinase 2 - metabolism
Medical research
Mice, Neurologic Mutants
microRNAs
MicroRNAs - metabolism
mir‐101
Neoplasm Invasiveness - physiopathology
Neoplasm Transplantation
Neoplastic Stem Cells - physiology
Original
Phosphatidylinositol 3-Kinases - metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Signal Transduction
Stem cells
Tumors
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Summary:Summary Background and aims 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. Methods and 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.
ISSN:1755-5930
1755-5949
DOI:10.1111/cns.12321