Open AccessmiR‐101 Acts as a Tumor Suppressor by Targeting Kruppel‐like Factor 6 in Glioblastoma Stem Cells
Author(s) -
Yao YiLong,
Ma Jun,
Wang Ping,
Xue YiXue,
Li Zhen,
Zhao LiNi,
Li ZhiQing,
Feng TianDa,
Liu YunHui
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12321
Subject(s) - gene knockdown , cancer research , chromatin immunoprecipitation , microrna , transcription factor , biology , stem cell , cancer stem cell , downregulation and upregulation , apoptosis , microbiology and biotechnology , promoter , gene expression , gene , genetics
Summary Background and aims Great interest persists in useful therapeutic targets in glioblastoma ( GBM ). Deregulation of microRNAs (mi RNA s) 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 ( GSC s) and the potential mechanisms. Methods and results Quantitative real‐time PCR showed that miR‐101 expression was decreased in GSC s. Overexpression of miR‐101 reduced the proliferation, migration, invasion, and promoted apoptosis of GSC s. One direct target of miR‐101, the transcription factor Kruppel‐like factor 6 ( KLF 6), 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 KLF 6 demonstrated by luciferase assays and chromatin immunoprecipitation assays. The downregulation of CHI3L1 led to the inactivation of MEK 1/2 and PI3K signal pathways. Furthermore, nude mice carrying the tumors of overexpressed miR‐101 combined with knockdown of KLF 6 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.