血小板外泌体来源反义LncRNA AS-PRR11调控结直肠癌恶性进展的机制研究

肿瘤相关血小板（TEP）调控结直肠癌（简称肠癌）进展机制尚不清楚。AS-PRR11（简称AP）是前期针对肠癌患者血小板外泌体测序、结合TCGA数据库筛选并命名的一个在血小板外泌体和肠癌组织中差异高表达的反义LncRNA。体外实验显示过表达AP能促进肠癌细胞增殖、侵袭和迁移；机制预实验和生信分析发现AP可结合多聚腺苷酸结合蛋白PABP2，进而增强癌基因PRR11的mRNA稳定性。故提出“TEP外泌体来源AP结合PABP2增强PRR11 mRNA稳定性，从而促进肠癌恶性进展“的科学假说。本项目拟结合体内外实验明确AP调控肠癌恶性进展的功能；利用GOF/LOF手段，设计拯救实验，阐明AP通过结合PABP2上调PRR11表达的分子机制；结合临床大样本验证AP/PABP2/PRR11信号轴与肠癌恶性进展的相关性。有关TEP外泌体来源AP在肠癌中的功能机制未见报道，本研究可为肠癌诊治提供新靶标。

Based on the results of high-throughput sequencing of tumor-educated platelet-derived exosomes, as well as the TCGA database-based bioinformatics analyses, we identified a novel antisense LncRNA AS-PRR11. We found that the level of LncRNA AS-PRR11 was increased in the tumor tissue of colorectal cancer patients, and may promote tumor proliferation, adhesion, and migration in vitro. Besides, overexpression/knockdown of LncRNA AS-PRR11 positively regulated the stability of the target gene ---- PRR11. But the underlying mechanism remains unclear. With the bioinformatics analysis and experimental verification, we identified that LncRNA AS-PRR11 might affect the protein stability by binding with the Polyadenylate-binding protein 2 (PABP2), and then participated in the post-transcriptional modification of PRR11, and thus affecting the pathological process of colorectal cancer. We will test this hypothesis by carrying out cell biological experiments and in vivo study. The results of this project will not only contribute to elucidate the pathogenesis of colorectal cancer further, but also provide a new target to diagnosis and treatment of colorectal cancer.