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长链非编码RNA NEAT1通过靶向PDPK1海绵化微小RNA-147的激活在曲克芦丁辐射防护中抑制辐射损伤。

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

作者信息

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

机构信息

School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong 277160, China.

Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China.

出版信息

iScience. 2023 Jan 5;26(2):105932. doi: 10.1016/j.isci.2023.105932. eCollection 2023 Feb 17.

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.

摘要

更好地理解辐射损伤背后lncRNA-miRNA-mRNA网络的分子机制可能有助于辐射防护。本研究旨在探讨lncRNA NEAT1、miR-147和磷酸肌醇依赖性蛋白激酶1(PDPK1)相互作用在曲克芦丁(TRT)辐射防护中的潜在作用。我们首先证明NEAT1可吸附miR-147,且PDPK1 mRNA是miR-147的主要靶标。在细胞中,辐射后NEAT1和PDPK1水平下调,但TRT处理后升高。miR-147水平在辐射后显著诱导,而在TRT处理后受到抑制。NEAT1负向调节miR-147的表达,而miR-147靶向PDPK1以下调其表达。在辐射防护中,TRT通过有效上调NEAT1来抑制miR-147并上调PDPK1。我们得出结论,TRT可通过刺激NEAT1抑制miR-147来上调PDPK1表达,从而促进辐射防护。NEAT1可能是辐射损伤的关键治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe20/9868541/db796f2d8510/fx1.jpg

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