MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells.
MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells.
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DOI：
10.1016/s1674-8301(10)60058-9
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发表时间：
2010-11
影响因子：
2.3
通讯作者：
Fu, Zhen
中科院分区：
文献类型：
--
作者：
Li, Ping;Lu, Xiaoming;Wang, Yingyi;Sun, Lihua;Qian, Chunfa;Yan, Wei;Liu, Ning;You, Yongping;Fu, Zhen
MicroRNAs调控肿瘤干细胞的自我更新和分化。在本研究中，我们试图鉴定miR-181b在胶质瘤干细胞中的表达，并探讨miR-181b对胶质瘤干细胞的生物学作用。实时荧光定量聚合酶链式反应(Real-time PCR)检测U87细胞分离的胶质瘤干细胞MIR-181b的表达。用miR-181b慢病毒表达载体在U87胶质瘤干细胞中高表达miR-181b和/或替莫唑胺处理后，进行二次神经球实验、软琼脂集落形成实验和四甲基偶氮唑盐比色法。与U87细胞相比，U87胶质瘤干细胞中miR-181b的表达显著降低。过表达miR-181b可减少U87胶质瘤干细胞在体外的神经球形成，并抑制软琼脂集落形成，并且在感染miR-181b慢病毒的U87胶质瘤干细胞中，细胞生长抑制率呈时间依赖性增加。此外，miR-181b对替莫唑胺诱导的次级神经球和软琼脂集落的抑制以及对细胞生长抑制率有协同作用。MIR-181b作为一种肿瘤抑制因子，在胶质瘤干细胞中抑制增殖并降低对替莫唑胺的化疗耐药性。
MicroRNAs regulate self renewal and differentiation of cancer stem cells. There, we sought to identify the expression of miR-181b in glioma stem cells and investigate the biological effect of miR-181b on glioma stem cells in this study. MiR-181b expression was measured by real-time PCR in glioma stem cells isolated from U87 cells by FACS sorting. After miR-181b was overexpressed in U87 glioma stem cells by miR-181b lentiviral expression vector and/or treatment of temozolomide, secondary neurosphere assay, soft agar colony assay and MTT assay were performed. Compared with U87 cells, the expression of miR-181b was significantly decreased in U87 glioma stem cells. Overexpression of miR-181b decreased neurosphere formation by U87 glioma stem cells in vitro and suppressed colony formation in soft agar, and the cell growth inhibition rates increased in a time-dependent manner in U87 glioma stem cells infected with miR-181b lentivirus. Furthermore, miR-181b had a synergistic effect on temozolomide-induced inhibition of secondary neurosphere and soft agar colony, and on cell growth inhibition rates. MiR-181b functions as a tumor suppressor that suppresses proliferation and reduces chemoresistance to temozolomide in glioma stem cells.