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

Okabe T1, Kumagai M2, Nakajima Y3, Shirotake S1, Kodaira K1, Oyama M1, Ueno M1, Ikeda M2. PLoS One. 2014;9(10):e109693.

1Department of Uro-oncology, Saitama Medical University International Medical Center, Saitama, Japan.and

2Department of Physiology, Saitama Medical University, Saitama, Japan; Molecular Clock Project, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.and

3Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Kagawa, Japan.

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.

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