胶质瘤是成人最常见原发性脑肿瘤，人巨细胞病毒（HCMV）与胶质瘤恶性程度、预后密切相关。肿瘤干细胞对放化疗抵抗所致术后复发是致死的关键，而SOX2是肿瘤干细胞重要标志，决定肿瘤恶性程度和放化疗抵抗。前期发现HCMV促进胶质瘤恶性生长并诱导SOX2表达。预实验发现SOX2促进HCMV基因表达，下调ND10关键组分PML和Sp100A。因此，提出SOX2通过下调PML和Sp100A促进HCMV复制，加剧胶质瘤进程。本项目拟构建SOX2过表达胶质瘤细胞系，明确SOX2对PML和Sp100A的调控、对HCMV复制和基因表达的影响；在胶质瘤细胞系验证PML和Sp100A抑制HCMV复制；用荧光素酶报告系统、ChIP、RNA-seq和Co-IP等解析SOX2下调PML和Sp100A的机制；再在临床样本和原代胶质瘤细胞中验证。揭示SOX2通过促进HCMV感染加剧胶质瘤恶性化的机制，为临床干预提供新靶点。

Glioma is the most common primary brain tumor in adults, HCMV is closely associated with its malignancy and prognosis. Postoperative recurrence caused by chemoradiotherapy resistance is a leading cause of death. As a leading biomarker of tumor stem cell, SOX2 determines the malignancy and the level of chemoradiotherapy resistance. We have previously elucidated that HCMV infection promotes glioma cell growth and SOX2 expression. The preliminary experiment of this project showed that SOX2 significantly promotes HCMV gene expression in glioma cells, and down-regulates PML and Sp100A, two key components of the host antiviral complex, ND10. Therefore, it is hypothesized that SOX2 exacerbates the glioma process by facilitating HCMV replication through down-regulation of PML and Sp100A. This project will construct SOX2 over-expressing glioma cell lines in order to clarify the role of SOX2 on HCMV gene expression and genome replication in glioma cells. We will illuminate the regulation mechanism of SOX2 on PML and Sp100A through ChIP, luciferase reporting system, RNA-seq and Co-IP et al.; and verify that PML and Sp100A inhibit HCMV replication in glioma cells; and validate the aforementioned hypotheses in clinical samples and primary glioma cells. This project will reveal the mechanism of SOX2 inducing glioma malignance through HCMV and provide new targets for clinical intervention. This project will reveal the mechanism of SOX2 promoting glioma malignancy through facilitating HCMV infection, so as to provide new targets for clinical intervention.