胶质瘤是发病率最高的颅内肿瘤，临床预后极差。发病机制尚不清楚。我们前期研究发现，癌基因EZH2在胶质瘤中高表达，其降低则能抑制胶质瘤增殖，且能下调CDK4和E2F1表达，提示EZH2对胶质瘤细胞周期与增殖发挥关键调控作用。miRNAs是重要的转录后调控分子，负向调控靶基因表达。我们前期研究提示：miR-138能有效抑制胶质瘤细胞增殖和阻遏细胞周期；而且发现miR-138抑制EZH2效力最佳，并能下调EGFR基因表达。因此，miR-138具有胶质瘤治疗的潜在价值。我们假设：miR-138与EZH2存在交互抑制作用；EZH2介导两条信号环路即：EZH2 - CDK4/6-pRB-E2F1与EZH2 - EGFR-E2F1促进胶质瘤演进；miR-138通过直接靶向抑制EZH2阻遏该信号环路，发挥抑制胶质瘤细胞增殖和侵袭的调控作用。因此，本研究将进一步揭示胶质瘤发生机制并为临床治疗提供新的治疗靶标

Glioma is the most common brain tumor with deadly poor clinical prognosis and its pathogenesis remains unclear. Our preliminary results showed that oncogene EZH2 was abundantly expressed in Glioma, down-regulating of which was responsible for inhibition of glioma cell proliferation and lower expression of CDK4 and E2F1. Herein, EZH2 exerts a vital regulation on cell cycle and proliferation of Glioma. MicroRNAs are important post-transcriptional regulators, which negatively modulate gene expression. Our previous study displayed that miR-138 could effectively suppress Glioma cell proliferation and arrest cell cycle. Moreover, miR-138 was potent to inhibit EZH2 and EGFR, which implicated a potential value for Glioma treatment. Taken together, we hypothesize that there exists a negative crosstalk between miR-138 and EZH2; EZH2 promotes Glioma progression by mediating two signal curcuit pathways: EZH2 - CDK4/6-pRB-E2F1 and EZH2 - EGFR-E2F1; through suppressing the two pathways by directly inhibiting EZH2, miR-138 plays a great role in cell cycle, proliferation and invading process of Glioma. Our research will be available to further unravel mechanisms of Glioma tumorigenesis and new targets for glioma clinical treatment.