The impact of HIF1α on the Per2 circadian rhythm in renal cancer cell lines

PLoS One. 2014 Oct 21;9(10):e109693. doi: 10.1371/journal.pone.0109693. eCollection 2014.

Abstract

In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1α increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1α may enhance the amplitude of the Per2 circadian rhythm.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Circadian Rhythm / genetics
  • Genes, Reporter
  • Genetic Vectors / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Messenger / metabolism
  • Transcription, Genetic

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Period Circadian Proteins
  • RNA, Messenger
  • Aryl Hydrocarbon Receptor Nuclear Translocator

Grants and funding

The authors have no support or funding to report.