胶质瘤是最常见的颅内原发肿瘤，其恶性生物学行为与Hedgehog信号通路的异常激活有关。课题组前期对220例胶质瘤患者临床资料和组织样本基因表达谱研究发现，长链非编码RNA NEAT1是胶质瘤独立预后因子，其表达水平与胶质瘤增殖、侵袭等恶性生物学行为及与胶质瘤分子分型相关，与Hedgehog信号通路转录密切相关。.本项目以上述结果为依托，研究NEAT1对胶质瘤恶性细胞生物学行为及化疗药物敏感性的影响；研究NEAT1通过PRC2复合物/DBHS蛋白家族对Hedgehog信号通路的调控及GLIs通过直接与NEAT1启动子区结合对其转录的影响；并构建不同NEAT1表达状态下编码基因mRNA和非编码基因RNA层面的复杂功能网络，体内外实验验证此调控网络间互作关系。本研究可揭示NEAT1对胶质瘤恶性生物学行为和Hedgehog信号通路的调控意义，为胶质瘤靶向治疗和分子标记物的确定提供实验依据。

Glioma is the most common primary brain tumor in adults. Aberrant activation of Hedgehog signaling pathway are extensively involved in the pathobiology and malignant progression of glioma. We profiled the lncRNA expression signatures in 220 gliomas, and identified that expression of NEAT1 was positively correlated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that NEAT1 was an independent prognostic factor in GBM patients. Moreover, NEAT1 was correlated with Hedgehog activity and GSEA analysis indicated that NEAT1 regulating-gene-sets were enriched in glioma malignancy, including proliferation, invasion (migration) and angiogenesis. .. Based on these studies, we aim to investigate the functional role of NEAT1 on glioma cells using NEAT1 RNAi and lentivirus system. Then, we investigate the latent mechanism of NEAT1 on Hedgehog activity via PRC2 complex or DBHS family and positive feedback regulation of GLIs on NEAT1. Whole transcriptom sequencing technology was used to establish the comprehensive regulatory network of NEAT1 on both mRNA/non-coding RNA and to identify the regulatory function of this network in vivo and in vitro. The present study may provide insides for understanding the comprehensive networks of NEAT1 in glioma and provide a new biomarker and treatment strategy for clinical glioma management.