MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin
MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin
复制标题
MicroRNA 145 增强胶质母细胞瘤干细胞对去甲氧基姜黄素的化疗敏感性
DOI：
10.2147/cmar.s210076
复制
发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Shi, Lei
中科院分区：
文献类型：
--
作者：
Qian, Chunfa;Wang, Bin;Shi, Lei
背景资料：胶质瘤干细胞（GSC）的存在被认为是导致无法治愈的多形性胶质母细胞瘤（GBM）发展的关键因素。GSC通常在化疗耐药性期间显示，除了姜黄素的组分脱甲氧基姜黄素（DMC），其先前已被证实抑制GSC增殖并诱导凋亡。目的：本研究的目的是确定DMC抗GSCs耐药的主要机制。患者和方法：采用qRT-PCR检测miR-145在胶质瘤患者和GSC中的表达，并将miR-145过表达载体转染GSC。然后，进行功能分析（体外和体内）以确认miR-145和DMC在GSC中的作用。免疫组化和Western blot检测相关蛋白。结果：miR-145在GSC中呈低表达，在体内外均能增强GSC对DMC的化疗敏感性。GSC中miR-145的上调导致DMC的细胞生长抑制和凋亡增加。进一步的机制研究表明，miR-145和DMC的联合作用可能参与了miR-145/SOX 2-Wnt/β-catenin通路。SOX 2的过表达降低了GSC对miR-145+ DMC处理的生长抑制的抗性。结论：我们的数据强烈支持miR-145通过靶向SOX 2-Wnt/β-catenin轴在增强GSC对DMC的化疗敏感性中的重要作用。
Background: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis. Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC. Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot. Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment. Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.