Identification of genes associated with poor prognosis

细胞周期蛋白依赖性激酶(CDK)抑制剂p27^1；Kip1&gt；是细胞的关键负性调节因子。P27；；Kip1&gt；降解激活G1期细胞周期蛋白-CDK复合体，促进细胞周期由G1期进入S期。许多临床研究表明，p27^&lt；Kip1&gt；在许多类型的人类癌症中表达降低，包括乳腺癌和结直肠癌，并与其高侵袭性和不良预后密切相关。P27；；Kip1和gt；在人类肿瘤中的表达水平降低是由于泛素-蛋白酶体途径促进了p27；；kip1和gt；的降解。研究表明，p27^lt；Kip1&gt；是一种SCF型泛素连接酶，它通过26S蛋白酶体泛素化p27^；lt；Kip1&gt；以泛素依赖的降解为靶点，促进p27^&lt；Kip1&gt；的降解，但在p27^&lt；Kip1&gt；-低表达的肿瘤中，其高侵袭性或预后不良的原因尚不清楚。为了解决这个问题，我们试图确定哪些基因的表达受到p27^；；Kip1&gt；-表达下调的影响。在本研究中，我们对人结肠癌细胞系HCT116进行了p27^；；Kip1&gt；基因的靶向性干扰，以期建立p27；；kip1&gt；低表达的模型细胞系。我们发现了一个基因PPAG4，它是由p27^&lt；Kip1&gt；-表达降低而诱导的。

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.