Department of Neurology, Liaocheng People's Hospital, Liaocheng City, Shandong Province, China.
IUBMB Life. 2021 Jul;73(7):916-926. doi: 10.1002/iub.2472. Epub 2021 Apr 27.
Emerging evidence has shown that Long noncoding RNAs (LncRNAs) are aberrantly expressed and functionally involved in the development of neurodegenerative disorders. In this work, we investigated the regulatory effects of lncRNA of LINC01311 and its competing endogenous RNA target of hsa-miR-146a-5p in a cellular model of Alzheimer's disease (AD). SH-SY5Y cells were treated with synthetic Βeta-Amyloid Peptide (1-42) (AB1-42) in vitro to induce AD-like neural injuries. Expressions of LINC01311 and hsa-miR-146a-5p were monitored by qRT-PCR. LINC01311 was upregulated and hsa-miR-146a-5p downregulated to examine their functional regulations on AB1-42-induced apoptosis, proliferation slowdown, autophagy, and amyloid precursor protein (APP) accumulations. Hsa-miR-146a-5p was also overexpressed in LINC01311-upregulated SH-SY5Y cells to examine their correlated regulations on AB1-42-induced neural injuries. LINC01311 was downregulated whereas hsa-miR-146a-5p upregulated in AB1-42 treated SH-SY5Y cells. LINC01311 upregulation and hsa-miR-146a-5p downregulation protected AB1-42-induced apoptosis, proliferation slowdown, autophagy, and APP accumulations in SH-SY5Y cells. Hsa-miR-146a-5p overexpression reversed the protection of LINC01311 on AB1-42-induced neural injuries. Our work demonstrated that the epigenetic axis of LINC01311/hsa-miR-146a-5p was involved in the functional regulation of human-lineage neurons in a cellular model of AD, thus suggesting a clinical potential of exploring epigenetic network for treating AD patients.
越来越多的证据表明，长链非编码 RNA（lncRNAs）表达异常，并在神经退行性疾病的发生发展中发挥功能作用。在这项工作中，我们研究了长链非编码 RNA LINC01311 的调控作用及其与 hsa-miR-146a-5p 的竞争内源性 RNA 靶点在阿尔茨海默病（AD）细胞模型中的作用。我们用合成的 Βeta-淀粉样肽（1-42）（AB1-42）体外处理 SH-SY5Y 细胞，诱导类似 AD 的神经损伤。用 qRT-PCR 监测 LINC01311 和 hsa-miR-146a-5p 的表达。上调 LINC01311，下调 hsa-miR-146a-5p，观察它们对 AB1-42 诱导的细胞凋亡、增殖减缓、自噬和淀粉样前体蛋白（APP）积累的功能调节作用。在 LINC01311 上调的 SH-SY5Y 细胞中过表达 hsa-miR-146a-5p，观察它们对 AB1-42 诱导的神经损伤的相关调节作用。在 AB1-42 处理的 SH-SY5Y 细胞中，LINC01311 下调，hsa-miR-146a-5p 上调。LINC01311 的上调和 hsa-miR-146a-5p 的下调可保护 AB1-42 诱导的 SH-SY5Y 细胞凋亡、增殖减缓、自噬和 APP 积累。hsa-miR-146a-5p 的过表达逆转了 LINC01311 对 AB1-42 诱导的神经损伤的保护作用。我们的工作表明，LINC01311/hsa-miR-146a-5p 的表观遗传轴参与了 AD 细胞模型中人源性神经元的功能调节，提示探索表观遗传网络治疗 AD 患者的临床潜力。
