Micro RNA Profiling in Pediatric Cancers

儿科癌症中的 Micro RNA 分析

• 批准号: 8157570
• 负责人: Javed Khan
• 金额: $ 12.11万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8157570
• 关键词: Malignant Childhood Neoplasm; MicroRNAs

Purpose: microRNAs have been shown to be involved in different human cancers. We therefore have performed expression profiles on a panel of pediatric tumors to identify cancerspecific microRNAs.We also investigated if microRNAs are coregulated with their host gene. Experimental Design: We performed parallel microRNAs and mRNA expression profiling on 57 tumor xenografts and cell lines representing 10 different pediatric solid tumors using microarrays. For those microRNAs that map to their host mRNA, we calculated correlations between them. Results: We found that the majority of cancer types clustered together based on their global microRNA expression profiles by unsupervised hierarchical clustering. Fourteen microRNAs were significantly differentially expressed between rhabdomyosarcoma and neuroblastoma, and 8 of them were validated in independent patient tumor samples. Exploration of the expression of microRNAs in relationship with their host genes showed that the expression for 43 of 68 (63%) microRNAs located inside known coding genes was significantly correlated with that of their host genes. Among these 43 microRNAs, 5 of 7 microRNAs in the OncomiR-1 cluster correlated significantly with their host gene MIRHG1 (P less than 0.01). In addition, high expression of MIRHG1 was significantly associated with high stage and MYCN amplification in neuroblastoma tumors, and the expression level of MIRHG1 could predict the outcome of neuroblastoma patients independently from the current neuroblastoma risk-stratification in two independent patient cohorts. Conclusion: Pediatric cancers express cancer-specific microRNAs. The high expression of the OncomiR-1 host gene MIRHG1 correlates with poor outcome for patients with neuroblastoma, indicating important oncogenic functions of this microRNAcluster in neuroblastoma biology. (Clin Cancer Res 2009;15(17):55608)

目的：已显示MicroRNA与不同的人类癌症有关。因此，我们已经在小儿肿瘤小组上进行了表达谱以鉴定特异性microRNA。 实验设计：我们对57种肿瘤异种移植物和细胞系进行了平行的microRNA和mRNA表达谱分析，并使用微阵列代表10种不同的小儿实体瘤。对于那些映射到其宿主mRNA的microRNA，我们计算了它们之间的相关性。结果：我们发现，大多数癌症类型通过无监督的分层聚类而根据其全球microRNA表达谱聚集在一起。在横纹肌肉瘤和神经母细胞瘤之间，有14个microRNA显着差异表达，其中8个在独立的患者肿瘤样品中得到了验证。探索与其宿主基因关系的microRNA的表达表明，位于已知编码基因内部的68（63％）microRNA中有43个（63％）的表达与其宿主基因的表达显着相关。在这43个microRNA中，Oncomir-1簇中的7个microRNA中有5个与其宿主基因miRHG1显着相关（P小于0.01）。此外，MIRHG1的高表达与神经母细胞瘤肿瘤中的高阶段和MYCN扩增显着相关，MIRHG1的表达水平可以预测神经细胞瘤患者的结果，独立于两个独立患者群体中当前的神经母细胞瘤风险分解。结论：小儿癌表达癌症特异性的microRNA。神经母细胞瘤患者的oncomir-1宿主基因miRHG1的高表达与较差的预后相关，表明该微生物肿瘤在神经母细胞瘤生物学中的重要致癌功能。 （Clin Cancer Res 2009; 15（17）：55608）