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BioDrugs

, Volume 28, Issue 1, pp 41–54 | Cite as

miR-125b Inhibitor May Enhance the Invasion-Prevention Activity of Temozolomide in Glioblastoma Stem Cells by Targeting PIAS3

  • Lei Shi
  • Yi Wan
  • Guan Sun
  • Shuguang Zhang
  • Zhimin WangEmail author
  • Yanjun ZengEmail author
Original Research Article

Abstract

Background

Temozolomide, an alkylating agent, is a promising chemotherapeutic agent for treating glioblastoma. Although chemotherapy with temozolomide may restrain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells maintaining these tumors persist. Previous research has shown that temozolomide can inhibit the proliferation of human glioblastoma stem cells (GSCs); however, no research has focused on the invasion of GSCs, which is an important factor for glioblastoma recurrence. Accumulating evidence indicates that microRNA (miR)-125b over-expression in GSCs may increase their invasiveness.

Objective

Our objective was to identify the effects and mechanism of action of an miR-125b inhibitor combined with temozolomide in the invasive pathogenesis of GSCs.

Methods

We modified the levels of miR-125b expression in primary GSCs in order to observe the effect on sensitivity to temozolomide on invasion, and we further analyzed the differences in mechanism between miR-125b treatment alone and treatment with miR-125b plus temozolomide using the Cancer PathwayFinder PCR Array.

Results

Our results demonstrated that either an miR-125b inhibitor or temozolomide could modestly inhibit the invasiveness of GSCs. Furthermore, GSCs that were pre-transfected with an miR-125b inhibitor, then treated with temozolomide, showed significantly decreased invasiveness when compared with GSCs treated with an miR-125b inhibitor or temozolomide alone. Further research into the underlying mechanism demonstrated that the miR-125b inhibitor enhanced the invasion-prevention activity of temozolomide in GSCs through targeting PIAS3 (protein inhibitor of activated STAT [signal transducer and activator of transcription]), which contributed to reduced STAT3 transcriptional activity and subsequent decreased expression of matrix metalloproteinase (MMP)-2 and -9.

Conclusions

miR-125b could play a role in the development of temozolomide resistance in GSCs. Inhibition of miR-125b expression may enhance sensitivity of GSCs to temozolomide by targeting PIAS3 on cell invasion.

Keywords

Reverse Transcription Polymerase Chain Reaction Temozolomide Temozolomide Treatment Glioblastoma Stem Cell Chemotherapeutic Sensitivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Funding

This work was supported by the China Natural Science Foundation (81000963 and 81201976), Jiangsu Province’s 333 Talent Program (BRA2011046), Jiangsu Province’s Natural Science Foundation (BK2012670), Medical Research Foundation by Jiangsu Province Health Department (YG201301 and Z201318), the Clinical Technology Development of Jiangsu University (JLY20120053), the Kunshan Social Development Foundation (KS1006, KS1009), and the Suzhou Social Development Foundation (SYS201063).

Conflicts of interest

All authors have declared the sources of research funding for this manuscript and have no financial or other contractual agreements that might cause (or be perceived as causes of) conflicts of interest.

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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe First People’s Hospital of Kunshan affiliated with Jiangsu UniversitySuzhouPeople’s Republic of China
  2. 2.Department of NeurosurgerySuzhou Kowloon Hospital affiliated with Shanghai Jiao Tong University School of MedicineSuzhouPeople’s Republic of China
  3. 3.Department of NeurosurgeryFourth Affiliated Yancheng Hospital of Nantong UniversityYanchengPeople’s Republic of China
  4. 4.Beijing University of TechnologyBeijingPeople’s Republic of China

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