Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Mol Neurosci. 2021 Jan;71(1):193-199. doi: 10.1007/s12031-020-01666-w. Epub 2020 Jul 13.
Long non-coding RNAs (lncRNAs) have regulatory roles in several aspects of cellular physiology. Recent studies have also revealed their role in neuronal differentiation and the pathophysiology of neurologic disorders such as epilepsy. We have recently reported altered expression of a number of lncRNAs in the peripheral blood of epileptic patients in association with their response to antiepileptic drugs. One the most significantly altered lncRNAs in epileptic patients is the antisense non-coding RNA in the INK4 locus (ANRIL), whose expression has been found to be higher in both refractory and non-refractory groups compared with controls. In the current study, we aimed to identify the methylation status of this lncRNA to suggest a potential mechanism for deregulated ANRIL expression. Thus, we assessed the methylation status of the ANRIL promoter in 40 patients with refractory epilepsy, 40 patients with non-refractory epilepsy and 40 normal controls using the high-resolution melting (HRM) method. The HRM results showed hypomethylation of the ANRIL promoter region in both refractory epilepsy and non-refractory epilepsy patients compared with normal controls. This methylation pattern was consistent with the recently reported upregulation of this lncRNA in patients with epilepsy. Thus, we suggest altered methylation of the ANRIL promoter as a potential cause of its aberrant expression in peripheral blood of epileptic patients.
长链非编码 RNA（lncRNAs）在细胞生理的多个方面具有调节作用。最近的研究还揭示了它们在神经元分化和神经障碍（如癫痫）的病理生理学中的作用。我们最近报道了癫痫患者外周血中许多 lncRNAs 的表达改变与其对抗癫痫药物的反应有关。在癫痫患者中改变最显著的 lncRNA 之一是 INK4 基因座的反义非编码 RNA（ANRIL），其表达在难治性和非难治性组中均高于对照组。在本研究中，我们旨在确定该 lncRNA 的甲基化状态，以提出其表达失调的潜在机制。因此，我们使用高分辨率熔解（HRM）方法评估了 40 例难治性癫痫患者、40 例非难治性癫痫患者和 40 例正常对照者的 ANRIL 启动子的甲基化状态。HRM 结果显示，难治性癫痫和非难治性癫痫患者的 ANRIL 启动子区域均呈低甲基化状态，与正常对照组相比。这种甲基化模式与最近报道的癫痫患者中该 lncRNA 的上调一致。因此，我们认为 ANRIL 启动子的改变甲基化可能是其在外周血中异常表达的潜在原因。
