MiR-15a and miR-16-1 cluster functions in human leukemia
MiR-15a and miR-16-1 cluster functions in human leukemia
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DOI：
10.1073/pnas.0800121105
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发表时间：
2008-04-01
影响因子：
11.1
通讯作者：
Croce, Carlo M.
中科院分区：
文献类型：
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作者：
Calin, George A.;Cimmino, Amelia;Croce, Carlo M.
microRNAs（miRNAs）是一类调控基因表达的短链非编码RNA，在人类疾病（包括癌症）中发挥重要作用。每种miRNA都被预测调控数百种转录物，但只有少数得到实验验证。在慢性淋巴细胞白血病（CLL）中，最常见的成人白血病，miR-15 a和miR-16-1在大多数情况下丢失或下调。在我们之前的工作表明miR-15 A/16-1通过靶向BCL 2癌基因的肿瘤抑制功能之后，在这里，我们在白血病细胞系模型（MEG-01）和原发性CLL样品中产生了由miR-15 a/6-1调节的基因的高通量谱。通过结合实验和生物信息学数据，我们在白血病细胞中鉴定了miR-15 a/6-1-基因签名。在miR-15 a/16-1特征的组分中，我们观察到富含AU的元素（战神）的统计学显著富集。通过检查基因本体（GO）数据库，发现直接或间接影响细胞凋亡和细胞周期的癌症基因（如MCL 1，BCL 2，ETS 1或JUN）显着富集。
MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15A/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/6-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/6-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (ARES). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.