Identification and analysis of functional RNAs regulated by p53 family members in gastrointestinal tumorigenesis

miR-200家族包括两个簇：位于1号染色体上的miR-200 b-200 a-429和位于12号染色体上的miR-200 c-141。我们确定了位于两个簇周围的响应元件，这些响应元件对p53家族有响应。在此，计算机模拟miRNA靶点预测将v-crk肉瘤病毒CT 10癌基因同源样（CRKL）鉴定为潜在的miR-200 b/200 c/429靶点。miR-200 b/200 c/429通过直接靶向CRKL的3 '-UTR区域来抑制CRKL的表达。重要的是，CRKL表达在引入野生型p53和TAp 63的癌细胞中降低。Oncomine数据库显示，与相应的正常组织相比，CRKL水平在多种癌症类型中显著过表达。我们还发现CRKL在携带突变型p53基因的原发性乳腺癌组织中过表达。我们的研究结果表明，p53诱导的miRNA，200 b/200 c/429是CRKL癌蛋白的负调控因子，并提出了一个新的p53-miR-200-CRKL通路在癌症发生。

The miR-200 family includes two clusters: miR-200b-200a-429 located on chromosome 1; and miR-200c-141 located on chromosome 12. We identified response elements located around both clusters that are responsive to p53 family. Here, in silico miRNA target prediction identified the v-crk sarcoma virus CT10 oncogene homolog-like (CRKL) as a potential miR-200b/200c/429 target. MiR-200b/200c/429 inhibits the expression of CRKL by directly targeting its 3'-UTR region. Importantly, CRKL expression was decreased in cancer cells with introduction of wild-type p53 and TAp63. Oncomine database shows that CRKL levels are significantly overexpressed in multiple cancer types compared with the corresponding normal tissues. We also found that CRKL was overexpressed in primary breast cancer tissues harboring mutant p53 genes. Our results indicate that a p53-inducible miRNA, 200b/200c/429 is a negative regulator of the CRKL oncoprotein and suggest a new p53-miR-200-CRKL pathway in carcinogenesis.