miRNA-374靶向PTTG基因抑制胶质瘤细胞的增殖和侵袭能力

摘要

[目的]研究微小RNA-374(microRNA-374,miR-374)对胶质瘤细胞增殖和侵袭能力的影响,并探讨其可能的机制.[方法]观察慢病毒过表达miR-374载体转染U251和U87细胞株后对肿瘤细胞增殖和侵袭能力的影响;双荧光素酶报告基因检测miR-374与PTTG基因的靶标关系;Western blot检测PTTG基因下游相关信号通路蛋白的表达水平.[结果]过表达miR-374可以显著抑制胶质瘤细胞的增殖和侵袭能力.双荧光素酶报告实验证实PTTG基因是miR-374的潜在靶基因,其下游的bFGF和PI3K信号通路等关键基因的表达也相应下调.[结论]miR-374高表达可通过靶向PTTG基因抑制胶质瘤细胞的增殖和侵袭.这一机制有可能为胶质瘤的基因治疗提供新的策略.%[Objective] To investigate the possible effect of microRNA-374 (miR-374) expression on tumor cells' proliferation and invasion and particular mechanism.[Methods] MiR-374 overexpression lentiviral vector (Lv-miR-374) and a control lentiviral empty vector (LEV) were stably transfected into human glioma U251 and U87 cells,to evaluate the effect of miR-374 on cell proliferation and invasion ability.Target relationship between miR-374 and PTTG were researched by dual luciferase report gene assay.Expression level of correlative signaling pathways of the downstream gene protein was analyzed by Western blot.[Results] We revealed that the overexpression of miR-374 dramatically suppressed glioma cell growth and invasion in vitro.Target relationship between miR-374 and PTTG was confirmed by dual luciferase report gene assay.And decreased protein expression of PTTG,bFGF,AKT,MMP2,and p70S6K was consistent with the effect of miR-374 overexpression.[Conclusion] Decreased miRNA-374 is an unfavorable prognosis marker and promotes glioma cell growth and invasion via direct targeting PTTG.Our findings provide new insights into the role of miR-374 in the development of gliomas,and implicate the potential application of miR-374 in cancer therapy.