Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers
Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers
复制标题
乳腺癌中新型 IGF1R 基因内反义非编码 RNA 的异常等位基因开关印记
DOI：
10.1016/j.ejca.2014.10.031
复制
发表时间：
2015-01-01
影响因子：
8.4
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Kang, Lihua;Sun, Jingnan;Li, Wei
胰岛素样生长因子I型受体（IGF1R）在乳腺癌中经常失调，但其分子机制尚不清楚。最近，利用RNA引导的染色质构象捕获（R3C）在造血恶性肿瘤中发现了IGF1R位点内的一种新的基因内长链非编码RNA (lncRNA) IRAIN。在乳腺癌组织中，我们发现与IGF1R编码mRNA相比，IRAIN lncRNA是从内含子启动子以反义方向转录的。与IGF1R编码RNA不同，这种非编码RNA是印迹的，具有来自父本等位基因的单等位基因表达。在具有rs8034564单核苷酸多态性信息的乳腺癌组织中，存在两个亲本等位基因的不平衡表达，其中“G”基因型比“A”基因型更有利。在乳腺癌患者中，IRAIN在肿瘤和外周血白细胞中都有异常的印迹，表现出一种等位基因开关模式：正常组织中表达的等位基因失活，正常印迹的等位基因表达。表观遗传学分析显示，该基因启动子的CpG岛存在广泛的DNA去甲基化。这些数据表明IRAIN lncRNA是一种在乳腺癌中异常调控的新型印迹基因。(C) 2014 Elsevier Ltd.版权所有。
The insulin-like growth factor type I receptor (IGF1R) is frequently dysregulated in breast cancers, yet the molecular mechanisms are unknown. A novel intragenic long non-coding RNA (lncRNA) IRAIN within the IGF1R locus has been recently identified in haematopoietic malignancies using RNA-guided chromatin conformation capture (R3C). In breast cancer tissues, we found that IRAIN lncRNA was transcribed from an intronic promoter in an antisense direction as compared to the IGF1R coding mRNA. Unlike the IGF1R coding RNA, this non-coding RNA was imprinted, with monoallelic expression from the paternal allele. In breast cancer tissues that were informative for single nucleotide polymorphism (SNP) rs8034564, there was an imbalanced expression of the two parental alleles, where the 'G' genotype was favorably imprinted over the 'A' genotype. In breast cancer patients, IRAIN was aberrantly imprinted in both tumours and peripheral blood leucocytes, exhibiting a pattern of allele-switch: the allele expressed in normal tissues was inactivated and the normally imprinted allele was expressed. Epigenetic analysis revealed that there was extensive DNA demethylation of CpG islands in the gene promoter. These data identify IRAIN lncRNA as a novel imprinted gene that is aberrantly regulated in breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.