PTEN 5'UTR-45aa-uORF在神经胶质瘤中的抑癌功能及调控机制研究

抑癌基因PTEN基因在恶性胶质瘤中具有重要的生物学功能，但其作用方式与机制尚未完全清晰。申请人在PTEN mRNA的5’UTR区发现一个潜在的上游开放读码框(uORF)序列，前期结果表明该uORF在细胞内翻译一个全新的抑癌多肽PTEN-45aa。过表达PTEN-45aa可以显著抑制胶质瘤细胞在体外的生长与增殖。本项目拟研究：1）探索PTEN-45aa对胶质瘤细胞的作用方式与临床意义；2）研究PTEN-45aa的抑癌功能的详细分子机制；3）验证PTEN-45aa的临床转化的前景。通过本项目，我们希望对抑癌基因PTEN的在胶质瘤中的作用机制提供新的注释，拓宽人们对传统“非编码区”的认知，并最终为胶质瘤的靶向治疗提供有益的参考。

The tumor suppressor gene PTEN plays a pivotal role in malignant glioma. However, the way how it functions and the molecular mechanism is still to be understood. The applicant discovered a potential uORF at the 5’UTR of PTEN mRNA, which translated a new tumor suppressive polypeptide PTEN-45aa. Preliminary studies showed that overexpression of PTEN-45aa significantly suppressed proliferation and growth of glioma cells in vitro. Thus, this study will focus on: 1) Investigate the function of PTEN-45aa and its clinical significance; 2) Study the detailed molecular mechanism of the tumor suppressor PTEN-45aa; 3) Verify the clinical translational potential of PTEN-45aa. Through this study, we hope to provide a new annotation to the function of the tumor suppressor gene PTEN, enrich the knowledge of traditional “untranslated regions”, and finally provide instructive reference for targeted therapy of malignant glioma.