Long noncoding RNA THRIL contributes in lipopolysaccharide-induced HK-2 cells injury by sponging miR-34a (Retracted article. See vol. 122, 2021)
Long noncoding RNA THRIL contributes in lipopolysaccharide-induced HK-2 cells injury by sponging miR-34a (Retracted article. See vol. 122, 2021)
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DOI：
10.1002/jcb.27354
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Xiao, Ying
中科院分区：
文献类型：
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作者：
Deng, Yao;Luan, Sen;Xiao, Ying
系统性红斑狼疮（SLE）是一种病因不明的慢性自身免疫性疾病。近年来，一些长链非编码RNA（longnoncodingRNA，lncRNA）已被报道参与SLE的分子改变。本研究旨在探讨TNF相关和HNRNPL相关免疫调节lncRNA（THRIL）在SLE中的作用。将人上皮HK-2细胞暴露于脂多糖（LPS）以模拟体外SLE模型。检测THRIL、miR-34 a和单核细胞趋化蛋白-1（MCP-1）的功能及其相关性。LncRNA THRIL在LPS刺激的细胞中高度表达，并且THRIL过表达加重LPS诱导的细胞损伤，因为细胞活力降低，细胞凋亡和促炎细胞因子的释放增加。THRIL作为microRNA-34 a（miR-34 a）的海绵，可以直接靶向MCP-1。此外，MCP-1激活JNK和Wnt/β-catenin信号通路。结论：lncRNA THRIL可能是LPS诱导HK-2细胞损伤的重要调控因子。THRIL过表达可能通过吸收miR-34 a，从而阻止MCP-1被miR-34 a降解而加重LPS诱导的细胞损伤。THRIL/miR-34 a/MCP-1轴可能在SLE发病中起重要作用。
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown etiology. Nowadays, several long noncoding RNAs (lncRNAs) have been reported as molecular alterations involved in SLE. This study aimed to reveal the function of TNF-related and HNRNPL-related immunoregulatory lncRNA (THRIL) in SLE. Human epithelial HK-2 cells were exposed to lipopolysaccharide (LPS) to mimic an in vitro SLE model. Then, the functions of THRIL, miR-34a, and monocyte chemoattractant protein-1 (MCP-1), as well as their correlations were detected. LncRNA THRIL was highly expressed in the LPS-stimulated cells, and THRIL overexpression aggravated LPS-induced cell damage as cell viability was decreased, and apoptosis and the release of proinflammatory cytokines were increased. THRIL worked as a sponge of microRNA-34a (miR-34a) and it could directly target MCP-1. Furthermore, MCP-1-activated JNK and Wnt/-catenin signaling pathways. In conclusion, this study suggested that lncRNA THRIL might be a key regulator participating in LPS-induced injury in HK-2 cells. THRIL overexpression aggravated LPS-induced injury possibly via sponging miR-34a, and thus preventing MCP-1 from degradation by miR-34a. The THRIL/miR-34a/MCP-1 axis might play critical roles in SLE.