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长链非编码 RNA ILF3-AS1 通过抑制海马 miR-212 的表达介导癫痫的发生。

LncRNA ILF3-AS1 mediated the occurrence of epilepsy through suppressing hippocampal miR-212 expression.

机构信息

Department of Neurology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

Aging (Albany NY). 2020 May 13;12(9):8413-8422. doi: 10.18632/aging.103148.

Abstract

Increased expression of some matrix metalloproteinases (MMPs) is closely associated with epilepsy. However, factors that promote their expression have not been clarified. Long noncoding RNAs (lncRNAs) play crucial roles in the development of human diseases, including various cancers, but its potential function in temporal lobe epilepsy (TLE) has remained unexplored. In this study, we showed that hippocampal and serum ILF3-AS1 levels are higher in TLE patients than in matched controls. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced ILF3-AS1 expression in astrocytes, while ectopic expression of ILF3-AS1 enhanced IL-6 and TNF-α expression. Ectopic ILF3-AS1 in astrocytes also increased expression of MMP2, MMP3, MMP9 and MMP14, but suppressed expression of miR-212. Consistent with that finding, miR-212 levels were lower in the hippocampus and serum of TLE patients than their controls. This suggests that ILF3-AS1 promotes expression of inflammatory cytokines and MMPs by targeting miR-212 and that ILF3-AS1 plays a crucial role in the development of TLE.

摘要

某些基质金属蛋白酶(MMPs)的表达增加与癫痫密切相关。然而,促进其表达的因素尚未阐明。长链非编码 RNA(lncRNA)在人类疾病的发展中起着至关重要的作用,包括各种癌症,但它在颞叶癫痫(TLE)中的潜在功能仍未被探索。在这项研究中,我们表明 TLE 患者的海马体和血清 ILF3-AS1 水平高于匹配对照组。白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α诱导星形胶质细胞中 ILF3-AS1 的表达,而 ILF3-AS1 的异位表达增强了 IL-6 和 TNF-α的表达。星形胶质细胞中的异位 ILF3-AS1 还增加了 MMP2、MMP3、MMP9 和 MMP14 的表达,但抑制了 miR-212 的表达。与这一发现一致,TLE 患者海马体和血清中的 miR-212 水平低于对照组。这表明,ILF3-AS1 通过靶向 miR-212 促进炎症细胞因子和 MMPs 的表达,并且 ILF3-AS1 在 TLE 的发展中起着至关重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d219/7244033/7c0ace5e8143/aging-12-103148-g001.jpg

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