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

CNS Neuroscience and Therapeutics - Tập 21 Số 1 - Trang 40-51 - 2015
Yilong Yao1, Jun Ma2,3, Ping Wang2,3, Yixue Xue2,3, Zhen Li1, Li‐Ni Zhao2,3, Zhiqing Li2,3, Tian‐Da Feng1, Yunhui Liu1
1Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
2Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China
3Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China

Tóm tắt

SummaryBackground and aimsGreat 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 resultsQuantitative 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.ConclusionsOur findings provided a comprehensive analysis of miR‐101 and further defining it as a potential therapeutic candidate for GBM.

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CNS Neuroscience and Therapeutics

Tập 21 Số 1

40-51

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