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

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

doi:10.1016/j.isci.2023.105932

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

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

Authors

Yong-Jian Hu^{1

2}, Gui-Yuan Song^{1

3

4}, Fan Zhang^{1

2}, Nan Zhang¹, Fei Wang¹, Jing-Long Wang¹, Xia Wang⁵, Tao-Yang Wang^{1

2}, Yu-Feng Li⁴, Yi-di Yan⁶, Wen-Tao Dou⁶, Chen-Yi Cheng⁶, Ping Xu^{1

2}

Affiliations

¹ School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong 277160, China.
² Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China.
³ School of Public Health, Weifang Medical University, Weifang, Shandong 261000, China.
⁴ Radiology Laboratory, Central Laboratory, Rizhao People's Hospital, Rizhao, Shandong 276800, China.
⁵ College of Medical Laboratory, Xinxiang Medical University, Xinxiang, Henan 453003, China.
⁶ Basic Medical School, Xinxiang Medical University, Xinxiang, Henan 453003, China.

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.

Keywords: Biological sciences; Cell biology; Molecular biology; Molecular mechanism of gene regulation.