IDH1 as a frequently mutated gene has potential effect on exosomes releasement by epigenetically regulating P2RX7 in intrahepatic cholangiocarcinoma

Biomed Pharmacother. 2019 May:113:108774. doi: 10.1016/j.biopha.2019.108774. Epub 2019 Mar 16.

Abstract

Biliary tract cancers (BTCs) was heterogeneous and characterized by late diagnosis and fatal outcome. To identify new biomarkers for BTCs, we performed Robust Rank Aggreg (RRA) analysis and identified that IDH1 mutation was common in ICC, while IDH1R132C was the most frequent type. Moreover, we identified P2RX7 and other 45 genes as downregulated genes with hypermethylation in IDH1R132C mutated cells. The WGCNA results predicted that P2RX7 could influence cholangiocarcinoma by exosomes related manners. Finally, we confirmed that P2RX7 was downregulated in IDH1R132C mutated cells as well as the expression of CD9 and CD81 by experiments. In conclusion, IDH1R132C mutation was relatively prevalent in ICC. P2RX7 might be a potential downstream gene and it might be related to exosomes releasement.

Keywords: Exosomes; Gene mutation; IDH1; Intrahepatic cholangiocarcinoma; P2RX7.

MeSH terms

  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Cell Line, Tumor
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • DNA Methylation / genetics
  • Down-Regulation
  • Epigenesis, Genetic
  • Exosomes / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Mutation
  • Receptors, Purinergic P2X7 / genetics*

Substances

  • P2RX7 protein, human
  • Receptors, Purinergic P2X7
  • Isocitrate Dehydrogenase
  • IDH1 protein, human