中文摘要
miRNA在各种肿瘤发展过程中有重要作用,但尚未有研究从miRNA成熟过程调控的角度,来对其在胃癌发生发展中的作用进行深入的机制研究。DDX家族基因能够特异性结合miRNA前体,使之最终加工成成熟miRNA。本研究通过解旋酶家族基因DDX18在miRNA-21成熟过程中的调控机制入手,提出了DDX18通过调控miRNA-21成熟,并影响下游PTEN/AKT通路来促进胃癌进展的合理假设。初步的研究结果已显示DDX18基因在胃癌组织中显著高表达,并与胃癌恶性生物学行为有关的病理特征和不良预后相关;干扰DDX18的表达可以使胃癌细胞AGS的增殖、克隆形成和小鼠异体移植瘤生长受到抑制;并通过small RNA-seq筛选出与DDX18表达相关的miRNA-21。基于上述结果,我们设计了相关实验来对DDX18通过调控miRNA-21成熟促进胃癌发展的分子机制进行验证。
英文摘要
MiRNA play an important role in tumor progression. However, there are not yet any study on the mechanism of the view of miRNA maturation in gastric cancer progression. DDX family can specially combined with pri-miRNA and promotes miRNA maturation. The study make a reasonable hypothesis that DDX18 regulates miRNA-21 maturation and affect downstream PTEN/AKT pathway in gastric cancer progression. Preliminary results show that DDX18 was high expression in gastric cancer tissue, and also related to the adverse pathological feature and poor prognosis. Interfering DDX18 expression could inhibits proliferation and colony formation of gastric cancer cell AGS. MiRNA-21 has been picked up through small RNA-seq. Based on the previous result, we design some experiments to prove the molecular mechanism that DDX18 regulates miRNA-21 maturation and promotes gastric cancer progression.
