miR-125b Inhibitor May Enhance the Invasion-Prevention Activity of Temozolomide in Glioblastoma Stem Cells by Targeting PIAS3
miR-125b Inhibitor May Enhance the Invasion-Prevention Activity of Temozolomide in Glioblastoma Stem Cells by Targeting PIAS3
复制标题
miR-125b 抑制剂可能通过靶向 PIAS3 增强替莫唑胺对胶质母细胞瘤干细胞的侵袭预防活性
DOI：
10.1007/s40259-013-0053-2
复制
发表时间：
2014-02-01
期刊：
影响因子：
6.8
通讯作者：
Zeng, Yanjun
中科院分区：
文献类型：
--
作者：
Shi, Lei;Wan, Yi;Zeng, Yanjun
BackgroundTemozolomide, 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.ObjectiveOur objective was to identify the effects and mechanism of action of an miR-125b inhibitor combined with temozolomide in the invasive pathogenesis of GSCs.MethodsWe 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.ResultsOur 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.ConclusionsmiR-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.
