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LncRNA GAS5 promotes apoptosis as a competing endogenous RNA for miR-21 via thrombospondin 1 in ischemic AKI
Cell Death Discovery ( IF 6.1 ) Pub Date : 2020-04-02 , DOI: 10.1038/s41420-020-0253-8
Xuemei Geng 1 , Nana Song 1 , Shuan Zhao 1 , Jiarui Xu 1 , Yong Liu 2 , Yi Fang 1 , Mingyu Liang 2 , Xialian Xu 1 , Xiaoqiang Ding 1
Affiliation  

Mounting evidence has indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) played important roles in renal ischemia/reperfusion (I/R) injury. However, the involvement of lncRNA growth arrest specific 5 (GAS5) in acute kidney injury (AKI) remained largely unexplored. This study aimed to determine possible mechanisms of GAS5 in the renal I/R process. We found that GAS5, noticeably upregulated by renal I/R injury, was further suppressed by delayed IPC while knockdown of miR-21 in vivo before IPC could significantly increased the GAS5 levels. Concurrently, TSP-1 was negatively regulated by miR-21 in vivo and vitro. Additionally, Reciprocal repression of GAS5 and miR-21 was identified. Knockdown of miR-21 in H6R0.5 treated HK-2 cells promoted apoptosis. Co-transfection of miR-21 mimic and pcDNA-GAS5 or pcDNA-Vector were performed, results of which showed that inhibition of miR-21 on TSP-1 could be rescued by overexpression of GAS5. This study suggested that GAS5 facilitated apoptosis by competitively sponging miR-21, which negatively regulated TSP-1 in renal I/R injury. This novel regulatory axis could act as a therapeutic target for AKI in the future.



中文翻译:

LncRNA GAS5 在缺血性 AKI 中作为 miR-21 的竞争性内源性 RNA 通过血小板反应蛋白 1 促进细胞凋亡

越来越多的证据表明,长链非编码 RNA (lncRNA) 和 microRNA (miRNA) 在肾缺血/再灌注 (I/R) 损伤中发挥重要作用。然而,lncRNA 生长停滞特异性 5 (GAS5) 在急性肾损伤 (AKI) 中的作用仍未得到充分探索。本研究旨在确定 GAS5 在肾 I/R 过程中的可能机制。我们发现,肾缺血再灌注损伤显着上调的 GAS5 被延迟的 IPC 进一步抑制,而 IPC 之前体内敲低 miR-21 可以显着增加 GAS5 水平。同时,TSP-1 在体内和体外均受到 miR-21 的负调控。此外,还发现了 GAS5 和 miR-21 的相互抑制。H6R0.5 处理的 HK-2 细胞中 miR-21 的敲低促进了细胞凋亡。进行miR-21模拟物与pcDNA-GAS5或pcDNA-Vector的共转染,结果表明miR-21对TSP-1的抑制可以通过GAS5的过表达来挽救。这项研究表明,GAS5 通过竞争性海绵 miR-21 促进细胞凋亡,而 miR-21 在肾缺血再灌注损伤中负向调节 TSP-1。这种新颖的调节轴可以作为未来 AKI 的治疗靶点。

更新日期:2020-04-24
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