Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER), 41013 Seville, Spain.
Int J Mol Sci. 2020 Aug 2;21(15):5534. doi: 10.3390/ijms21155534.
Hirschsprung disease (HSCR) is a neurocristopathy defined by intestinal aganglionosis due to alterations during the development of the Enteric Nervous System (ENS). A wide spectrum of molecules involved in different signaling pathways and mechanisms have been described in HSCR onset. Among them, epigenetic mechanisms are gaining increasing relevance. In an effort to better understand the epigenetic basis of HSCR, we have performed an analysis for the identification of long non-coding RNAs (lncRNAs) by qRT-PCR in enteric precursor cells (EPCs) from controls and HSCR patients. We aimed to test the presence of a set lncRNAs among 84 lncRNAs in human EPCs, which were previously related with crucial cellular processes for ENS development, as well as to identify the possible differences between HSCR patients and controls. As a result, we have determined a set of lncRNAs with positive expression in human EPCs that were screened for mutations using the exome data from our cohort of HSCR patients to identify possible variants related to this pathology. Interestingly, we identified three lncRNAs with different levels of their transcripts (, and ) between HSCR patients and controls. We propose such lncRNAs as possible regulatory elements implicated in the onset of HSCR as well as potential biomarkers of this pathology.
先天性巨结肠（HSCR）是一种神经嵴病，其特征是肠无神经节，这是由于肠神经系统（ENS）发育过程中的变化引起的。在 HSCR 的发病机制中，已经描述了涉及不同信号通路和机制的广泛分子。其中，表观遗传机制越来越受到重视。为了更好地理解 HSCR 的表观遗传基础，我们通过 qRT-PCR 对来自对照和 HSCR 患者的肠前体细胞（EPC）中的长非编码 RNA（lncRNA）进行了分析。我们旨在检测 84 个 lncRNA 中是否存在一组 lncRNA，这些 lncRNA 先前与 ENS 发育的关键细胞过程有关，并确定 HSCR 患者与对照组之间的可能差异。结果，我们确定了一组在人 EPC 中有阳性表达的 lncRNA，并用我们的 HSCR 患者队列的外显子组数据筛选这些 lncRNA 的突变，以鉴定可能与这种病理相关的变体。有趣的是，我们在 HSCR 患者和对照组之间发现了三个转录本水平不同的 lncRNA（、和）。我们提出这些 lncRNA 作为可能参与 HSCR 发病的调节因子，以及该病理的潜在生物标志物。
