Analgesic effects of microRNA-129-5p against bone cancer pain through the EphB1/EphrinB2 signaling pathway in mice

J Cell Biochem. 2019 Mar;120(3):2876-2885. doi: 10.1002/jcb.26605. Epub 2018 Nov 30.

Abstract

The study aims to investigate the analgesic effects of microRNA-129-5p (miR-129-5p) on bone cancer pain (BCP) by targeting Eph receptor B1 (EphB1) through the EphB1/EphrinB2 signaling pathway. BCP mice models were established, and C3H/HeJ female mice were classified into the normal, blank, negative control (NC), miR-129-5p mimics, miR-129-5p inhibitors, EphB1 knockout (KO), and miR-129-5p inhibitors + EphB1 KO groups. Quantitative reverse transcription polymerase chain reaction and Western blot analysis were used to evaluate the miR-129-5p expression, and messenger RNA (mRNA) and protein expressions of EphB1, p-EphB1, EphrinB2, and p-EphrinB2. EphB1 and EphrinB2 were highly activated in the tibias of BCP mice 7 days after the operation. EphB1 is a target gene of miR-129-5p. The mechanical withdrawal threshold increased in the miR-129-5p mimics, EphB1 KO and miR-129-5p inhibitors + EphB1 KO groups, but decreased in the miR-129-5p inhibitors group. Compared with the blank and the NC groups, the expression of miR-129-5p was significantly increased in the miR-129-5p mimics group, and the mRNA and protein expressions of EphrinB2, p-EphrinB2, EphB1, and p-EphB1 were significantly decreased, while in the miR-129-5p inhibitors group, the results were opposite (all P < 0.05); the mRNA and protein expressions of EphrinB2, p-EphrinB2, EphB1, and p-EphB1 were significantly decreased in the EphB1 KO group (all P < 0.05); the expression of miR-129-5p was significantly decreased in the miR-129-5p inhibitors + EphB1 KO group ( P < 0.05), while the mRNA and protein expressions of EphrinB2 and p-EphrinB2 were not significantly different ( P > 0.05). The results indicated that upregulated miR-129-5p alleviate BCP via downregulation of the EphB1/EphrinB2 signaling pathway.

Keywords: EphB1/EphrinB2 signaling pathway, microRNA-129-5p; analgesic effects; bone cancer pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Base Sequence
  • Bone Neoplasms / complications*
  • Cancer Pain / etiology*
  • Cancer Pain / genetics*
  • Cancer Pain / physiopathology
  • Ephrin-B1 / genetics
  • Ephrin-B1 / metabolism*
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism*
  • Female
  • Gene Expression Regulation
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pain Threshold
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Tibia / diagnostic imaging
  • Tibia / pathology

Substances

  • Ephrin-B1
  • Ephrin-B2
  • MIRN129 microRNA, mouse
  • MicroRNAs
  • RNA, Messenger