1 Division of Nephrology, State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University , Guangzhou, People's Republic of China .
2 Department of Pathology, Nanfang Hospital, Southern Medical University , Guangzhou, People's Republic of China .
Antioxid Redox Signal. 2018 Aug 1;29(4):355-376. doi: 10.1089/ars.2017.7278. Epub 2018 Mar 12.
Altered activities of long noncoding RNAs (lncRNAs) have been implicated in the regulation of microRNAs. microRNA-27a (miR-27a) upregulation has been shown to induce endoplasmic reticulum (ER) stress podocyte injury in diabetic nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of miR-27a with long intergenic noncoding RNA 1619 (LINC01619) and the target gene.
LINC01619 downregulation was found in human DN renal biopsy tissues and contributed to proteinuria and diminished renal function. LINC01619 was expressed in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619 exerted biological function by serving as a "sponge" for miR-27a, which negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In diabetic rats and high-glucose cultured podocytes, LINC01619 triggered oxidative stress and podocyte injuries as demonstrated by increased apoptosis, diffuse podocyte foot process effacement, and decreased renal function. Innovation and Conclusion: This study demonstrates that LINC01619 functions as a competing endogenous RNA and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury in DN. Antioxid. Redox Signal. 29, 355-376.
长链非编码 RNA（lncRNAs）的活性改变已被认为参与了 microRNAs 的调控。已有研究表明，microRNA-27a（miR-27a）的上调可诱导糖尿病肾病（DN）中的内质网（ER）应激足细胞损伤。在此，我们旨在探讨 miR-27a 与长基因间非编码 RNA 1619（LINC01619）及其靶基因之间相互调节的网络。
在人类 DN 肾活检组织中发现 LINC01619 下调，并与蛋白尿和肾功能减退有关。LINC01619 在足细胞细胞质中表达，并参与 ER 应激信号通路。LINC01619 通过充当 miR-27a 的“海绵”发挥生物学功能，miR-27a 负向靶向叉头框蛋白 O1（FOXO1）并激活 ER 应激。在糖尿病大鼠和高糖培养的足细胞中，LINC01619 引发氧化应激和足细胞损伤，表现为细胞凋亡增加、足细胞足突广泛消失和肾功能下降。
本研究表明，LINC01619 作为竞争性内源性 RNA，调节 DN 中 miR-27a/FOXO1 介导的 ER 应激和足细胞损伤。抗氧化还原信号 29,355-376。
