Down regulation of miR-143 promotes radiation - Induced thymic lymphoma by targeting B7H1

Toxicol Lett. 2017 Oct 5:280:116-124. doi: 10.1016/j.toxlet.2017.07.891. Epub 2017 Jul 20.

Abstract

MicroRNA-143 has been implicated in tumor metastasis by directly targeting Bcl-2, and microRNA-143 expression is decreased in several human tumors. However, the expression and targets of miR-143 in radiation carcinogenesis remain unclear. We found that the expression of miR-143 is down-regulated and the expression of B7H1 (Pdcd1) is up-regulated in radiation-induced thymic lymphoma model in BALB/c mice. Additionally, overexpression of miR-143 strongly inhibited cell proliferation and increased cell apoptosis and its down-regulation promoted cell proliferation and reduced cell apoptosis. We also determined that there is an inverse correlation between miR-143 expression and B7H1 protein expression in radiation-induced thymic lymphoma samples, and miR-143 targets B7H1 in a 3'UTR-dependent manner. In addition, we found that adenovirus over-expression of pre-miR-143 reduced tumorigenesis in vivo. Finally, we conclude that down-regulated expression of miR-143 and up-regulation of its direct target B7H1 may indicate a novel therapeutic method for radiation-induced thymic lymphoma by increased expression of miR-143 or inhibition of B7H1.

Keywords: B7H1; Radiation carcinogenesis; Radiation induced thymic lymphoma (RITL); Tumor therapy; miR-143.

MeSH terms

  • Animals
  • Apoptosis
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Lymphoma / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA / genetics
  • RNA / metabolism
  • Thymus Neoplasms / metabolism*

Substances

  • B7-H1 Antigen
  • MicroRNAs
  • MIRN143 microRNA, mouse
  • RNA