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