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目的:探讨miR-219-5p对人脑成胶质细胞瘤(glioblastoma,GBM)的恶性表型——增殖、凋亡和侵袭的影响,初步寻找与miR-219-5p发挥抑癌作用有关的靶点基因。方法:在60例GBM组织中分析miR-219-5p表达水平及mRNA表达谱,筛选与miR-219-5p表达量呈负相关的mRNA;选取前50个相关性最大的mRNA,用基因功能分析软件DAVID从中筛选出与GBM恶性进展相关的2组mRNA;最后用4个在线靶点预测网站从这2组中预测miR-219-5p的潜在靶点。采用MTT法、流式细胞术和Transwell实验初步验证miR-219-5p对GBM细胞增殖、凋亡和侵袭的影响。结果:60例GBM组织中筛出14个与增殖和凋亡相关的基因和5个与侵袭相关的基因(P<0.001);在这19个候选基因中预测到4个基因(TWIST1、MYO1B、WEE1和SPRED2)是miR-219-5p的潜在靶点。实验初步证明,miR-219-5p能够抑制GBM细胞的增殖和侵袭以及促进细胞凋亡(P<0.05)。结论:MiR-219-5p可能通过作用于多个靶点对GBM的恶性表型起到抑制作用。
Objective: To investigate the effect of miR-219-5p on the malignant phenotype-proliferation, apoptosis and invasion of human glioblastoma (GBM), and to find out the possible mechanism of miR-219-5p Target gene. Methods: The expression of miR-219-5p and its mRNA expression were analyzed in 60 cases of GBM tissues, and the mRNAs that were negatively correlated with the expression of miR-219-5p were screened. The top 50 mRNAs were selected and analyzed by gene function analysis The software DAVID screened 2 sets of mRNAs related to the malignant progression of GBM. Finally, 4 online target prediction websites were used to predict potential targets of miR-219-5p from these 2 groups. The effects of miR-219-5p on proliferation, apoptosis and invasion of GBM cells were preliminarily verified by MTT assay, flow cytometry and Transwell assay. Results: Sixty-four GBM tissues were screened for proliferation and apoptosis-related genes and five invasion-related genes (P <0.001). Four of the 19 candidate genes were predicted (TWIST1, MYO1B, WEE1 and SPRED2) are potential targets for miR-219-5p. Preliminary experiments show that miR-219-5p can inhibit the proliferation and invasion of GBM cells and promote apoptosis (P <0.05). Conclusion: MiR-219-5p may inhibit the malignant phenotype of GBM by acting on multiple targets.