LncRNA HOTAIR 负调控 miR-217 促进脑胶质母细胞瘤生长及其机制研究

Glioma is the most common tumor in cerebrum. Astroglioblastoma could be divided into four grades based on differentiation. Glioblastoma is the worst differentiated type that mainly appeared in male over 40. Its median survival is only 12-15 months, and the 5-year overall survival is only 5%. Cell cycle and cancer stem cell play important role in glioblastoma oncogenesis and development. HOTAIR is a type of lncRNA with antisense function. It is involved in multiple tumors proliferation, metastasis, and drug resistance through PRC2 and LSD1. miR-217 is a kind of tumor suppressor miRNA receiving widely attention. In this study, we aim to analyze the role of HOTAIR impact on glioblastoma proliferation mediated by miR-217 to regulate cell cycle and cancer stem cell from cell, animal, and clinical sample levels through RNA interference, overexpression, flow cytometry, and xenograft mouse model.

脑胶质母细胞瘤(GBM)是脑胶质瘤中分化最差的类型，严重影响患者的生活质量及预后。已有研究发现，肿瘤细胞周期改变及干细胞形成在胶质母细胞瘤的发生发展过程中具有重要作用，但机制尚未完全阐明。HOTAIR是一种具有反义功能的lncRNA,可参与影响多种肿瘤的增殖、迁移等生物学行为。我们前期研究显示，lncRNA HOTAIR可以调控GBM细胞周期运行，从而促进GBM细胞增殖。生物信息学分析显示，HOTAIR可作为ceRNA与miR-217结合，从而抑制miR-217具有的肿瘤抑制作用。据此，我们提出“HOTAIR通过负调控miR-217促进胶质母细胞瘤的生长”的假说。我们拟通过RNAi、过表达、荧光素酶实验、裸鼠成瘤等技术，从临床样本、细胞、动物等分析证实HOTAIR可通过负调控miR-217促进胶质母细胞瘤的细胞周期运行及肿瘤干细胞形成，从而促进GBM增殖，为脑胶质瘤治疗提供新的靶点和策略。

脑胶质母细胞瘤(GBM)是脑胶质瘤中分化最差的类型，严重影响患者的生活质量及预后。已有研究发现，肿瘤细胞周期改变及干细胞形成在胶质母细胞瘤的发生发展过程中具有重要作用，但机制尚未完全阐明。HOTAIR是一种具有反义功能的lncRNA,可参与影响多种肿瘤的增殖、迁移等生物学行为。我们前期研究显示，lncRNA HOTAIR可以调控GBM细胞周期运行，从而促进GBM细胞增殖。生物信息学分析显示，HOTAIR可作为ceRNA与miR-217结合，从而抑制miR-217具有的肿瘤抑制作用。据此，我们提出“HOTAIR通过负调控miR-217促进胶质母细胞瘤的生长”的假说。我们拟通过RNAi、过表达、荧光素酶实验、裸鼠成瘤等技术，从临床样本、细胞、动物等分析证实HOTAIR可通过负调控miR-217促进胶质母细胞瘤的细胞周期运行及肿瘤干细胞形成，从而促进GBM增殖，为脑胶质瘤治疗提供新的靶点和策略。