转录因子TCF21调控PI3K-AKT途径影响非小细胞肺癌细胞生物学特性的研究

近年来新发现的抑癌基因TCF21抑癌机理未明，我们研究发现其在非小细胞肺癌中低表达，肺癌细胞系外源表达TCF21能显著抑制细胞增殖、迁移，促进凋亡。蛋白组学发现TCF21过表达显著下调PI3K-AKT通路重要成员AKT1/2，PPP2R4等基因表达。我们假设：TCF21可能通过转录抑制AKT1/2、PPP2R4等靶基因影响PI3K-AKT信号通路，发挥抑癌基因的作用。本项目拟通过临床样本分析中总结TCF21与上述各靶基因表达量以及与PI3K-AKT信号通路活化状态在非小细胞肺癌中的临床相关性，并将通过系列分子生物学实验解析TCF21调控PI3K-AKT信号通路各候选靶基因的分子机制，并通过移植瘤动物模型深入研究TCF21调控PI3K-AKT信号通路和抑制肿瘤增殖、迁移，促进凋亡的机制。结果不仅有助于阐明TCF21在NSCLC中的抑癌机制，而且将为非小细胞肺癌的防治提供新的思路。

In recent years, the mechanism of tumor suppressor gene TCF21 is unknown. We found that its low expression in non-small cell lung cancer. Exogenous expression of TCF21 in lung cancer cell lines can significantly inhibit cell proliferation, migration and promote apoptosis. Proteomics showed that TCF21 overexpression significantly down-regulated the expression of AKT1/2,PPP2R4, an important member of PI3K-AKT pathway. We hypothesized that TCF21 may affect the PI3K-AKT signal pathway and play the role of tumor suppressor genes through transcriptional inhibition of target genes such as AKT1/2 and PPP2R4. The purpose of this project is to summarize the clinical correlation between TCF21 and the expression of the above target genes and the activation of PI3K-AKT signaling pathway in non-small cell lung cancer through clinical sample analysis, and to analyze the molecular mechanism of TCF21 regulating the candidate target genes of PI3K-AKT signal pathway through a series of molecular biology experiments, and to deeply study the regulation of PI3K-AKT signal pathway and inhibition of tumor proliferation and migration by TCF21 through the animal model of transplanted tumor. The mechanism of promoting apoptosis. The results will not only help to clarify the anti-cancer mechanism of TCF21 in NSCLC, but also provide ideas for the prevention and treatment of non-small cell lung cancer.