The competing endogenous RNA network of CYP4Z1 and pseudogene CYP4Z2P exerts an anti-apoptotic function in breast cancer

FEBS Lett. 2017 Apr;591(7):991-1000. doi: 10.1002/1873-3468.12608. Epub 2017 Mar 16.


The competing endogenous RNA network (ceRNET) is involved in tumorigenesis and has become a hot spot of research. The ceRNET between CYP4Z1 and the pseudogene CYP4Z2P promotes angiogenesis and mediates tamoxifen resistance in breast cancer. Nevertheless, the effects of this ceRNET on cell apoptosis and related mechanisms remain unclear. In the present study, we found that downregulation of CYP4Z1 or the CYP4Z2P 3'-UTR promotes cell apoptosis, mirroring the functions of human telomerase reverse transcriptase (hTERT). Furthermore, the ceRNET between CYP4Z1 and pseudogene CYP4Z2P modulates hTERT expression by operating as a sub-ceRNET for hTERT. Our data demonstrate that the ceRNET between CYP4Z1 and pseudogene CYP4Z2P acts as a sub-ceRNET for hTERT and, thus, inhibits breast cancer apoptosis.

Keywords: hTERT; CYP4Z1; CYP4Z2P; apoptosis; ceRNET.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics*
  • Base Sequence
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cytochrome P450 Family 4 / genetics*
  • Cytochrome P450 Family 4 / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics
  • Pseudogenes / genetics*
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Telomerase / genetics
  • Telomerase / metabolism


  • 3' Untranslated Regions
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • CYP4Z1 protein, human
  • Cytochrome P450 Family 4
  • TERT protein, human
  • Telomerase