Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer
Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer
复制标题
对异常表达 miRNA 的全基因组筛选揭示了乳腺癌中的 miRNA 谱特征
DOI：
10.1007/s11033-012-2277-5
复制
发表时间：
2013-03-01
影响因子：
2.8
通讯作者：
Chen, Feng
中科院分区：
文献类型：
--
作者：
Guo, Li;Zhao, Yang;Chen, Feng
MiRNAs表达的失调导致了许多人类癌症的发生和发展。在此，我们试图通过应用高通量测序技术来获得miRNA表达谱与乳腺癌之间的潜在关联。对来自7对肿瘤和邻近正常组织的小RNA进行了测序。为了确定miRNA在组织和血清中的表达谱，对来自20名患者和30名正常女性的另外5份等量混合的血清样本进行了测序。尽管在样本中大量表达的miRNA数量相似，但我们检测到不同的miRNA表达谱。一些miRNAs在不同的肿瘤组织中表现出不一致或相反的失调趋势，包括一些大量表达的miRNA基因簇和基因家族。配对样本分析的Wilcoxon符号等级检验显示，异常的miRNAs在七个肿瘤样本中显示出更高水平的变异。我们还根据相对表达水平完整地调查了混合数据集中在肿瘤组织和血清组织中表达的异常miRNAs。其中大部分miRNAs在肿瘤组织中表达显著下调，但9个异常miRNAs(miR-18a、19a、20a、30a、103b、126、126*、192、1287)在肿瘤组织和血清中持续表达。基于实验验证的靶mRNAs的功能富集性分析表明，这些异常的miRNAs和miRNA组(miRNA基因簇和基因家族)在多种生物学过程中发挥着重要作用。MiRNA的动态表达谱、各种异常的miRNA谱以及miRNA调控网络的复杂性表明，miRNA表达谱是一种潜在的用于人类疾病分类或检测的生物标志物。
Dysregulation in the expression of miRNAs contributes to the occurrence and development of many human cancers. We herein attempted to obtain the potential association between miRNA expression profile and breast cancer by applying high-throughput sequencing technology. Small RNAs from seven paired tumor and adjacent normal tissue samples were sequenced. To determine the miRNA expression profiles in tissues and sera, another five equally pooled serum samples from 20 patients and 30 normal women were sequenced. Despite a similar number in abundantly expressed miRNAs across samples, we detected varying miRNA expression profiles. Some miRNAs showed inconsistent or opposite dysregulation trends across different tumor tissues, including some abundantly expressed miRNA gene clusters and gene families. Wilcoxon sign-rank test for paired samples analysis revealed that abnormal miRNAs showed a higher level of variation across the seven tumor samples. We also completely surveyed abnormal miRNAs expressed in tumor and serum tissues in the mixed datasets based on the relative expression levels. Most of these miRNAs were significantly down-regulated in tumor samples, but nine abnormal miRNAs (miR-18a, 19a, 20a, 30a, 103b, 126, 126*, 192, 1287) were consistently expressed in tumor tissues and serum samples. Based on experimentally validated target mRNAs, functional enrichment analysis indicated that these abnormal miRNAs and miRNA groups (miRNA gene clusters and gene families) have important roles in multiple biological processes. Dynamic miRNA expression profiles, various abnormal miRNA profiles and complexity of the miRNA regulatory network reveal that the miRNA expression profile is a potential biomarker for classifying or detecting human disease.