miRNA-374靶向PTTG基因抑制胶质瘤细胞的增殖和侵袭能力

MiRNA-374 Inhibits Glioma Cell Growth,Invasion Via Direct Targeting Pituitary Tumor Transforming Gene

【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 prolifer- ation and invasion ability. Target relationship between miR-374 and PTYG were researched by dual luciferase report gene assay. Ex- pression 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.