iScience (Feb 2023)

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

Journal volume & issue
Vol. 26, no. 2
p. 105932

Abstract

Read online

Summary: 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