A new and important relationship between miRNA-147a and PDPK1 in radiotherapy

J Cell Biochem. 2018 Apr;119(4):3519-3527. doi: 10.1002/jcb.26523. Epub 2018 Jan 11.

Abstract

It was found that the expression level of miR-147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR-147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR-147 (a or b) and PI3K/AKT signaling pathway. miR-147a overexpression plasmid and PDPK1 3'UTR luciferase reporter gene plasmid were constructed. Dual luciferase reporter gene system validation experiments were carried out on miR-147a and PDPK1 relationship. The verification experiments were also carried out. Bioinformatics analysis showed that there is a miR-147a binding site in the non-coding region (3'UTR) of PDPK1. In the experimental groups transfected with wild type PDPK1 gene of 3'UTR plasmid, the luciferase activity decreased (or increased) significantly in miR-147a (or inhibitor) group compared with miR-NC (or anti-miR-NC); There was no significant difference between the miR-147a group (or inhibitor) and the miR-NC group (or anti-miR-NC) in the transfection of PDPK1-3'UTR-Mut gene vector. PDPK1 was a target gene for direct regulation of miR-147a downstream. Verifying test results showed that the expression of PDPK1 mRNA and protein was reduced after overexpression of miR-147a, which was up-regulated after silencing miR-147a in TC, and V79 cells. These results suggest that miR-147a could be involved in the regulation of PDPK1 transcription by binding to the target site in PDPK1 mRNA 3'UTR, and then regulated AKT.

Keywords: PDPK1; miRNA-147a; plasmid; radiation; target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3-Phosphoinositide-Dependent Protein Kinases / genetics*
  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism*
  • Animals
  • Cells, Cultured
  • Computational Biology
  • Cricetinae
  • HEK293 Cells
  • Humans
  • Immunoblotting
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Protein Binding / radiation effects
  • Signal Transduction / drug effects

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • 3-Phosphoinositide-Dependent Protein Kinases
  • PDPK1 protein, human