miR-374b-5p在黄芩素抑制人肝癌细胞增殖中的作用及分子机制

项目名称： miR-374b-5p在黄芩素抑制人肝癌细胞增殖中的作用及分子机制

项目编号： No.81503310

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 别蓓蓓

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： 黄芩素具有广泛的抗肿瘤活性，研究发现miRNA可参与中药的抗肿瘤效应，但其是否参与黄芩素的抗肿瘤作用还未见报道。本课题组前期采用miRNA芯片分析发现肝癌细胞中miR-374b-5p的表达与黄芩素处理浓度呈负相关，生物信息学分析显示其与靶基因PTEN及AKT/mTOR通路相关，为此我们提出“黄芩素→下调miR-374b-5p表达→上调抑癌基因PTEN表达→抑制AKT/mTOR通路→抑制肝癌细胞增殖”的假设。本研究拟通过对比miR-374b-5p过表达和沉默细胞株经黄芩素处理后的增殖、凋亡、周期、裸鼠成瘤情况的变化；明确miR-374b-5p对PTEN和AKT/mTOR通路的调节作用；并检测PTEN、AKT的变化对黄芩素抑制肝癌细胞增殖的影响，从而证实提出的假设，旨在从miRNA角度研究黄芩素抗肝癌作用，为揭示黄芩素抗肝癌效应的分子机制提供新线索和新思路，为黄芩素药物开发和应用提供理论依据。

中文关键词： 黄芩素；肝细胞癌；微小RNA；细胞增殖；分子机制

英文摘要： Baicalein has been proved to possess significant antitumor activity. It has been demonstrated that the microRNA (miRNA) plays important roles in the antitumor effect of traditional Chinese herbs. However, the role of miRNA on the antitumor effect of baicalein has not been reported. Our previous study found that the expression of miR-374b-5p in hepatoma cells was negatively correlated with concentration of baicalein by miRNA microarray analysis. The bioinformatics analysis implies PETN, a tumor suppressor gene, is the potential target gene of miR-374b-5p, it is indicated that miR-374b-5p might be correlated with AKT/mTOR signaling pathway. To prove the hypothesis of “baicalein → down-regulation of miR-374b-5p → up-regulation of PTEN → suppression of AKT/mTOR pathway → proliferation inhibition of hepatoma cells”, we will investigate the cell proliferation, cell cycle, apoptosis of HCC through over-expressed miR-374b-5p and knockdown miR-374b-5p, validate the pathway that miR-374b-5p suppress AKT/mTOR signaling via PTEN, and analysis the effect of change of PTEN, AKT expression on the proliferation inhibition induced by baicalein. This Program will provide new clues and new ideas for revealing the molecular mechanism of anti-hepatoma of baicalein from miRNA perspective, and will provide a basis of development and application of baicalein.

英文关键词： Baicalein;hepatocarcinoma cell;microRNA;proliferation;molecular mechanism