Integrated Analysis Reveals hsa-miR-142 as a Representative of a Lymphocyte-Specific Gene Expression and Methylation Signature.
Integrated Analysis Reveals hsa-miR-142 as a Representative of a Lymphocyte-Specific Gene Expression and Methylation Signature.
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DOI：
10.4137/cin.s9037
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发表时间：
2012
影响因子：
2
通讯作者：
Anastassiou D
中科院分区：
文献类型：
--
作者：
Andreopoulos B;Anastassiou D
基因表达谱分析提供了对不同癌症类型的见解，并揭示了组织特异性表达特征。microRNA表达的改变有助于许多类型的人类疾病的发病机制。很少有研究整合了所有水平的基因表达，miRNA和甲基化，以揭示这些数据类型之间的相关性。我们进行了综合分析，以发现与多种癌症类型的基因表达和DNA甲基化特征相关的miRNA实例。使用来自癌症基因组图谱（TCGA）的数据，我们揭示了相同样本中与microRNA hsa-miR-142相关的一致基因表达和甲基化特征。在检查的所有癌症类型中，我们发现了基因组R和甲基化位点M的共表达的特征，其与hsa-miR-142的表达正相关（M+）或负相关（M-）。集合R始终包含许多基因，例如TRAF 3 IP 3、NCKAP 1 L、CD 53、LAPTM 5、PTPRC、EVI 2B、DOCK 2、LCP 2、CYBB和FYB。这种特征在胶质母细胞瘤、卵巢癌、乳腺癌、结肠癌、肾癌、肺癌、子宫癌和直肠癌中得以保留。在胶质母细胞瘤（GBM）和卵巢癌之间有28%的M甲基化位点重叠。GBM和卵巢之间的R基因有60%的重叠（P = 1.3e−11）。已知R中的大多数基因在淋巴细胞和造血干细胞中表达，而M反映了参与细胞-细胞粘附功能的膜蛋白。我们推测，hsa-miR-142相关的签名可能是造血特异性过程和甲基化事件积累的信号，触发细胞-细胞粘附的进行性丧失。我们还观察到，属于前神经亚型的GBM样本往往具有低表达的hsa-miR-142和R基因，低甲基化的M+和高甲基化的M-，而间充质样本具有相反的特征。
Gene expression profiling has provided insights into different cancer types and revealed tissue-specific expression signatures. Alterations in microRNA expression contribute to the pathogenesis of many types of human diseases. Few studies have integrated all levels of gene expression, miRNA and methylation to uncover correlations between these data types. We performed an integrated profiling to discover instances of miRNAs associated with a gene expression and DNA methylation signature across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), we revealed a concordant gene expression and methylation signature associated with the microRNA hsa-miR-142 across the same samples. In all cancer types examined, we found a signature of co-expression of a gene set R and methylated sites M, which correlate positively (M+) or negatively (M−) with the expression of hsa-miR-142. The set R consistently contains many genes, such as TRAF3IP3, NCKAP1L, CD53, LAPTM5, PTPRC, EVI2B, DOCK2, LCP2, CYBB and FYB. The signature is preserved across glioblastoma, ovarian, breast, colon, kidney, lung, uterine and rectum cancer. There is 28% overlap of methylation sites in M between glioblastoma (GBM) and ovarian cancer. There is 60% overlap of genes in R between GBM and ovarian (P = 1.3e−11). Most of the genes in R are known to be expressed in lymphocytes and haematopoietic stem cells, while M reflects membrane proteins involved in cell-cell adhesion functions. We speculate that the hsa-miR-142 associated signature may signal haematopoietic-specific processes and an accumulation of methylation events triggering a progressive loss of cell-cell adhesion. We also observed that GBM samples belonging to the proneural subtype tend to have underexpressed hsa-miR-142 and R genes, hypomethylated M+ and hypermethylated M−, while the mesenchymal samples have the opposite profile.