miR-96通过PDCD4调控胶质母细胞瘤放疗耐受的机制研究

Glioblastoma (GBM) is the most malignant tumor of nervous system, and radiotherapy is one of the conventional treatments. However, the molecular mechanisms of the tumorigenesis and radiosensitivity of GBM remain elusive. Our previous study found that miR-96 may contribute to the radioresistance of GBM by targeting 3’-UTR of PDCD4. We surpose that miR-96 regulate the radioresistance of GBM by targeting PDCD4. Further study showed that miR-96 were regulated by HIF-1α. This programs aim to find out the mechanism of miR-96 contribute to the radioresistance of GBM in vivo and in vitro, and study the upstream and downstream of miR-96. Based on the preliminary study, we will 1 miR-96 enhances the radioresistance of GBM via targeting PDCD4 3’-UTR;2 HIF-1α regulates the expression of miR-96. Taken together, this project studies the molecular mechanisms of miR-96 enhanced radioresistance of GBM; providing a scientific basis for individual therapy in GBM.

胶质母细胞瘤（GBM）是发病率最高、预后最差的恶性脑肿瘤，研究GBM放疗耐受机制是当前的热点和难点。我们前期采用miRNAs表达谱结合相关分子生物学实验，发现miR-96可能参与GBM的放疗耐受，这种作用的发挥可能依赖于调控PDCD4。由此，我们推测miR-96通过PDCD4调控GBM的放疗耐受。进一步的研究发现，在GBM中miR-96可能受HIF-1α的调控，进而使得放疗后miR-96的表达升高。本项目欲通过临床标本、细胞及动物水平，深入研究miR-96对GBM放疗耐受的作用及机制，探讨miR-96在GBM中的上、下游调控，阐明① miR-96可靶向作用于PDCD4进而增强GBM放疗耐受；②在GBM中miR-96受HIF-1α的调控。该研究有助于为增强GBM放疗效果提供新的靶点，更有助于为未来临床个体化治疗提供帮助。

胶质母细胞瘤（GBM）是发病率最高、预后最差的恶性脑肿瘤，研究GBM放疗耐受机制 是当前的热点和难点。我们前期采用miRNAs表达谱结合相关分子生物学实验，发现miR-96 可能参与GBM的放疗耐受，这种作用的发挥可能依赖于调控PDCD4。由此，我们推测miR-96 通过PDCD4调控GBM的放疗耐受。进一步的研究发现，在GBM中miR-96可能受HIF-1α的调控 ，进而使得放疗后miR-96的表达升高。本项目通过前期的研究，深入研 究miR-96对GBM放疗耐受的作用及机制，探讨miR-96在GBM中的上、下游调控，阐明① miR -96可靶向作用于PDCD4进而增强GBM放疗耐受；②在GBM中miR-96受HIF-1α的调控。该研 究有助于为增强GBM放疗效果提供新的靶点，更有助于为未来临床个体化治疗提供帮助。