Identification of genes associated with poor prognosis

细胞周期蛋白依赖性激酶（CDK）抑制剂p27 α<Kip1>充当细胞的关键负调节剂。p27 β的降解<Kip1>激活G1期细胞周期蛋白-CDK复合物，以促进细胞周期从G1期进展到S期。许多临床研究已经表明，<Kip1>在许多类型的人类癌症（包括乳腺癌和结肠直肠癌）中发现p27 α表达降低，并且与它们的高侵袭性和不良预后高度相关。人类癌症中p27 α表达水平的降低<Kip1>是由于p27 α<Kip1>通过泛素-蛋白酶体途径的降解增强。研究表明，p27 α的降解<Kip1>由SCF α促进<Skp2>，SCF α是SCF型泛素连接酶，其<Kip1>通过26 S-蛋白酶体将p27 α泛素化以靶向泛素依赖性降解。然而，在p27 α低表达的肿瘤中，高侵袭性或不良预后的原因尚不清楚<Kip1>。为了解决这一问题，我们试图鉴定哪些基因的表达受到p27^ -表达降低的影响<Kip1>。在本研究中，我们对<Kip1>人大肠癌细胞系HCT 116中的人p27 β基因进行了靶向破坏，以建立p27 β低表达的模型细胞系<Kip1>。我们发现了一个基因，PPAG 4，它是由p27^ -表达的减少诱导<Kip1>的。

A cyclin-dependent kinase (CDK) inhibitor p27^<Kip1> acts as a critical negative regulator of the cell. Degradation of p27^<Kip1> activates G1 cyclin-CDK complexes to promote the cell cycle progression from the G1 to S phase. Many clinical studies have indicated that reduced expression of p27^<Kip1> is found in many types of human cancers, including breast and colorectal carcinomas and highly associated with their high aggressiveness and poor prognosis. The decreased level of p27^<Kip1> expression in human cancers is due to enhanced degradation of p27^<Kip1> via ubiquitin-proteasome pathway. It is demonstrated that degradation of p27^<Kip1> is promoted by SCF^<Skp2>, an SCF-type ubiquitin ligase, which ubiquitinates p27^<Kip1> to target ubiquitin-dependent degradation through the 26S-proteasome However, it is unknown the cause of high aggressiveness or poor prognosis in the tumors with low p27^<Kip1>-expression. To solve the mater, we tried to identify the genes which expressions were affected by the reduction of p27^<Kip1>-expression. In the present study, we performed targeted disruption of human p27^<Kip1> gene in HCT116, human colorectal carcinoma cell lines in order to establish a model cell line with low expression of p27^<Kip1>. We found a gene, PPAG4, which was induced by the reduction of p27^<Kip1>-expression.