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.
Yong-Jian Hu  1  2 Gui-Yuan Song  1  3  4 Fan Zhang  1  2 Nan Zhang  1 Fei Wang  1 Jing-Long Wang  1 Xia Wang  5 Tao-Yang Wang  1  2 Yu-Feng Li  4 Yi-di Yan  6 Wen-Tao Dou  6 Chen-Yi Cheng  6 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.
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