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MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells

机译:MiR-181b抑制U87胶质瘤干细胞中替莫唑胺的增殖并降低其化学耐药性

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摘要

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.
机译:MicroRNA调节癌症干细胞的自我更新和分化。在此研究中,我们试图鉴定miR-181b在神经胶质瘤干细胞中的表达,并研究miR-181b对神经胶质瘤干细胞的生物学作用。通过实时PCR在通过FACS分选从U87细胞分离的神经胶质瘤干细胞中测量MiR-181b表达。通过miR-181b慢病毒表达载体在U87胶质瘤干细胞中过表达miR-181b和/或替莫唑胺治疗后,进行继发性神经球测定,软琼脂集落测定和MTT测定。与U87细胞相比,U87神经胶质瘤干细胞中miR-181b的表达明显降低。 miR-181b的过表达在体外减少了U87胶质瘤干细胞的神经球形成,并抑制了软琼脂中的菌落形成,并且在感染miR-181b慢病毒的U87胶质瘤干细胞中,细胞生长抑制率以时间依赖性方式增加。此外,miR-181b对替莫唑胺诱导的继发性神经球和软琼脂菌落的抑制作用以及对细胞生长的抑制作用具有协同作用。 MiR-181b充当肿瘤抑制因子,可抑制神经胶质瘤干细胞中的增殖并降低对替莫唑胺的化学耐药性。

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