miRNA-182调控PER基因对胶质瘤干细胞的影响机制
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v7i2.13396
Abstract
目的:本项目拟通过改变miR-182与PER基因的表达水平,分析GSCs生物学行为及相关信号通路蛋白的活性,旨在探讨miR-182与PER基因在GSCs生物学行为中的调控作用明确其可能的分子作用机制,为胶质母细胞瘤的治疗带来新的靶点。方法:本项目拟首先采用qRT-PCR检测miRNA-182及PER基因在胶质瘤干细胞(GSCs)中的内源性表达,并通过沉默或过表达miR-182/PER基因的表达水平,验证其对GSCs生物学行为的影响;然后通过生物信息软件预测PER基因为miRNA-182靶基因,并通过双荧光素酶报告分析证实,进而采用共转染技术进一步证实miRNA-182对PER基因的调控,并阐明对GSCs的生物学行为的影响。最后基于GBM患者癌组织和癌旁组织分析miRNA-182、PER基因等与GSM恶性程度、生存时间之间的关联,验证体外实验结论。结果:试验研究结果显示,随着GBM分级水平的升高,miRNA-182表达水平逐渐上升,PER表达水平逐渐下降。沉默组miRNA-182零表达,PER表达水平最高;过表达组miRNA-182表达水平最高,PER表达最低;阴性对照(空载体)组,miRNA-182表达水平中等,PER表达水平中等。结论:证实miRNA-182在脑胶质瘤干细胞中的表达水平显著上升,PER基因在脑胶质瘤干细胞中的表达水平下降,miRNA-182沉默可促进PER蛋白的表达水平。证实miRNA-182沉默可抑制脑胶质瘤干细胞的增殖、迁移、侵袭,促进其细胞凋亡;miRNA-182过表达可促进脑胶质瘤干细胞的增殖、迁移、侵袭,抑制其细胞凋亡;证实miRNA-182过表达同时PER基因沉默可显著促进胶质瘤干细胞的增殖、迁移、侵袭,抑制其细胞凋亡,miR-182沉默同时PER过表达可抑制胶质瘤干细胞的增殖、迁移、侵袭,促进其细胞凋亡;证实PER基因是miRNA-182的靶基因;证实miRNA-182靶向调控生物钟核心基因PER,进而影响胶质瘤干细胞生物学行为,应用于临床价值很大。
Keywords
miRNA-182;PER基因;胶质瘤干细胞;增殖影响;机制研究
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