Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer
Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer
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DOI：
10.1073/pnas.0801615105
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发表时间：
2008-05-13
影响因子：
11.1
通讯作者：
Coukos, George
中科院分区：
文献类型：
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作者：
Zhang, Lin;Volinia, Stefano;Coukos, George
MicroRNAs （miRNAs）是一类丰富的小非编码rna，具有负基因调控功能。miRNA失调参与人类癌症的发生和发展；然而，潜在的机制及其对癌症全基因组转录变化的贡献在很大程度上仍然未知。我们通过综合基因组方法研究了miRNA在人上皮细胞[卵巢癌]中的失调，包括miRNA微阵列（n = 106）、基于阵列的比较基因组杂交（n = 109）、cDNA微阵列（n = 76）和组织阵列（n = 504）。miRNA表达在恶性转化和肿瘤进展过程中明显下调。基因组拷贝数缺失和表观遗传沉默分别可能导致晚期卵巢肿瘤中约15%和至少约36%的miRNA下调，miRNA下调有助于全基因组转录失调。最后，鉴定出位于14号染色体miRNA集群（Dlk1-Gtl2结构域）中的8个miRNA是潜在的肿瘤抑制基因。因此，我们的研究结果表明，mirna可能为上皮性卵巢癌提供新的生物标志物和治疗靶点。
MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelia[ ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of approximate to 15% and at least approximate to 36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.