长链非编码RNA Linc8910对胶质瘤干细胞增殖和自我更新的影响

Effects of Long Non-Coding RNA Linc8910 on Proliferation and Self-Renewal of Glioma Stem Cells

目的:通过非编码RNA测序筛选,发现在胶质瘤干细胞(GSC)中特异性高表达的长链非编码RNA,并研究其在GSC中的功能,为针对GSC的肿瘤治疗提供新的潜在靶点。方法:对不同胶质母细胞瘤患者来源的GSC和非干性肿瘤细胞进行RNA测序,鉴定到在GSC中特异性高表达的长链非编码RNA Linc8910。利用慢病毒感染体系在GSC中敲低Linc8910的表达,利用Q-PCR技术检测Linc8910的表达及敲低效果。通过检测GSC细胞活力评价Linc8910对GSC增殖的影响;通过检测肿瘤球形成能力评估Linc8910对GSC自我更新能力的影响。结果:Linc8910在T4121 GSC中显著高表达,GSC分化后Linc8910表达水平下降。应用不同干涉序列在T4121 GSC中敲低Linc8910导致GSC形成肿瘤球的能力以及细胞活力明显下降。结论:Linc8910在GSC中高表达,抑制Linc8910表达显著抑制GSC的增殖及自我更新能力,提示Linc8910在脑胶质瘤的发生发展中可能起着关键作用。

Objective:To screen the long non-coding RNA highly expressed in glioma stem cells(GSC)and in⁃vestigate their roles in GSC,providing novel potential targets for glioblastoma(GBM)therapy.Methods:RNA se⁃quencing was performed with multiple GBM patients derived GSC and the matched non-stem tumor cells.The long non-coding RNA Linc8910 was identified to be highly expressed in GSC.The expression of Linc8910 was knocked down by lentivirus infection and was examined by Q-PCR.The effect of Linc8910 on GSC proliferation was assessed by cell viability examination.The effect of Linc8910 on GSC self-renewal was evaluated by tumor sphere formation assay.Results:Linc8910 was highly expressed in T4121 GSC compared with the matched nonstem tumor cells.Depletion of Linc8910 with different shRNA sequences significantly inhibited GSC tumor sphere formation and cell proliferation.Conclusion:The long non-coding RNA Linc8910 is preferentially expressed in GSC.Depletion of Linc8910 compromises the cell growth and self-renewal of GSC,suggesting an important role of Linc8910 in GBM progression.