Activation of long-non-coding RNA NEAT1 sponging microRNA-147 inhibits radiation damage by targeting PDPK1 in troxerutin radioprotection

激活长链非编码 RNA NEAT1 海绵 microRNA-147 可通过靶向 PDPK1 在曲克芦丁放射防护中抑制辐射损伤

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作者:Yong-Jian Hu, Gui-Yuan Song, Fan Zhang, Nan Zhang, Fei Wang, Jing-Long Wang, Xia Wang, Tao-Yang Wang, Yu-Feng Li, Yi-di Yan, Wen-Tao Dou, Chen-Yi Cheng, Ping Xu

Abstract

A better understanding of the molecular mechanism involving the lncRNA-miRNA-mRNA network underlying radiation damage can be beneficial for radioprotection. This study was designed to investigate the potential role of lncRNA NEAT1, miR-147 and Phosphoinositide Dependent Protein Kinase 1 (PDPK1) interaction in radioprotection by troxerutin (TRT). We first demonstrated that NEAT1 sponged miR-147, and PDPK1 mRNA was the primary target of miR-147. In the cells, the NEAT1 and PDPK1 levels were downregulated after the radiation but increased after the treatment with TRT. The miR-147 level was significantly induced by radiation and inhibited by TRT. NEAT1 negatively regulated the expression of miR-147, whereas miR-47 targeted PDPK1 to downregulate its expression. In radioprotection, TRT effectively upregulated NEAT1 to inhibit miR-147 and to upregulate PDPK1. We concluded that TRT could promote radioprotection by stimulating NEAT1 to upregulate PDPK1 expression by suppressing miR-147. NEAT1 could be a critical therapeutic target of radiation damage.

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