脑胶质瘤是最常见的原发颅内肿瘤。p53信号通路与胶质瘤放疗所致DNA损伤修复密切相关，不同p53状态的胶质瘤对放疗的敏感性不同。丝氨酸/苏氨酸家族成员Wip1是一种新发现的癌基因，可以调节p53的功能，在放射损伤时显著上调。我们发现在胶质瘤中选择性过表达的Wip1基因与野生型p53的胶质瘤细胞生长密切相关。Wip1基因在DNA损伤修复中起重要作用，是决定细胞损伤后修复还是凋亡的一个重要因素。胶质瘤中少数的脑肿瘤干细胞是胶质瘤放疗抵抗的根源，并且放疗可能增加脑肿瘤干细胞的比例。Wip1基因与肿瘤干细胞的增殖和生长密切相关，但Wip1基因在脑肿瘤干细胞中表达及其对放疗的作用尚未见报道。本研究拟通过调控Wip1基因在脑肿瘤干细胞中的表达有效实现脑肿瘤干细胞的分化进而达到放疗增敏作用。通过本项目的实施，将帮助我们进一步认识胶质瘤放疗抵抗的机制，有望为胶质瘤的治疗提供新的靶点。

Gliomas are the most common primary human brain tumors. p53 pathway is a key regulator of glioma cell responses to DNA damage induced by radiation，and the p53 status determines the sensitivity of glioma cells to radiation. Wild-type p53-induced phosphatase 1 (Wip1) belongs to the Ser/Thr PP2C family of phosphatases.Wip1 is a newly found oncogene, can suppresso the activity of p53 and is up-regulated after radiation. Our prior discovery indicated that Wip1 is selectively over-expressed in gliomas with wild-type p53 and plays an important role in the proliferation in glioma cells. Wip1 acts as a key regulator to DNA damage and repair., is another factor that determine the cells are repaired or apoptotic when they are demaged. Brain tumor stem cells have been identified in gliomas and CD133 was identified as a marker for them. It was demonstrated that CD133+ cells contribute to glioma radio-resistance via preferential activation of DNA damage checkpoints and increase after radiation. Wip1 is related with proliferation and growth of stem cells, but the expression of Wip1 and the roles after radiation in brain tumor stem cells have not been reported yet. Our study intends to increase the sensitivity of brain tumor stem cells to radiation by controlling the expression of Wip1 to induce the differentiation of brain tumor stem cells. Our study with further reveals the mechanisms of glioma radio-resistance and provides a promising target for therapeutic intervention of glioma.