Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea.
These authors contributed equally to this work.
Mol Cells. 2021 Sep 30;44(9):658-669. doi: 10.14348/molcells.2021.0173.
Enhancers have been conventionally perceived as -acting elements that provide binding sites for -acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncoding RNA expression loci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, and led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as and (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.
增强子通常被认为是一种 - 作用元件，为 - 作用因子提供结合位点。然而，最近的研究表明，增强子是可转录的，这些转录本被称为增强子 RNA（eRNA），具有调节功能。在这里，我们通过对肝癌（HCC）细胞系中的非编码 RNA 表达基因座进行分析和确定与 eRNA 相关的组蛋白标记（如 H3K27ac 和 H3K4me1）之间的重叠，来鉴定推定的 eRNA。在 132 个源自 HCC 的非编码 RNA 中，有 74 个与 FANTOM 联盟定义的 eRNA 基因座重叠，有 65 个位于 TCGA 数据集正常组织和肿瘤组织之间差异表达基因的近端区域。有趣的是，两种选定的推定 eRNA（和）的敲低导致其靶 mRNA 的下调，以及 HCC 细胞增殖和迁移的减少。此外，在 TCGA 数据集的肿瘤样本中，这两种非编码 RNA 和靶 mRNA 的表达上调，高表达与患者的不良预后相关。总之，我们的研究表明，非编码 RNA 如（即推定的 eRNA）可以促进参与细胞增殖和分化的基因的转录，并且这些非编码 RNA 的失调可能导致 HCC 等癌症。
