Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Circadian Clock Genes, PER1 and PER2, as Tumor Suppressors

체내 시계 유전자 PER1과 PER2의 종양억제자 기능

  • Son, Beomseok (Department of Integrated Biological Science, Pusan National University) ;
  • Do, Hyunhee (Department of Biology Education, Korea National University of Education) ;
  • Kim, EunGi (Department of Integrated Biological Science, Pusan National University) ;
  • Youn, BuHyun (Department of Integrated Biological Science, Pusan National University) ;
  • Kim, Wanyeon (Department of Biology Education, Korea National University of Education)
  • 손범석 (부산대학교 일반대학원 생명시스템학과) ;
  • 도현희 (한국교원대학교 제3대학 생물교육학과) ;
  • 김은기 (부산대학교 일반대학원 생명시스템학과) ;
  • 윤부현 (부산대학교 일반대학원 생명시스템학과) ;
  • 김완연 (한국교원대학교 제3대학 생물교육학과)
  • Received : 2017.09.08
  • Accepted : 2017.10.25
  • Published : 2017.10.30
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Abstract

Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

암을 포함한 다양한 인간의 질병 발생이 circadian clock 유전자의 변형된 발현 양상과 깊은 연관관계를 나타내고 있다. 세포 주기와 세포 성장은 circadian rhythm과 연결되어 있으며, 이를 조절하는 clock 유전자의 비정상적인 발현은 결국 종양 발생과 암의 발달을 유발하게 된다. Circadian clock에 관한 분자적 기전은 다수의 clock activator와 clock repressor의 통합적인 조절에 따른 전사 및 번역이 포함된 음성피드백 고리로 구성되어 있다. 이러한 circadian rhythm의 자동조절 기전에 의해 전체 유전체의 약 10~15%가 전사 수준에서 영향받는 것으로 나타났다. 많은 clock 유전자들 중, Period 1 (Per1)과 Period 2 (Per2)는 clock repressor 유전자로 정상적인 생리적 리듬을 조절하는 것에 기여한다. PER1과 PER2는 cyclin, CDK, CKI를 포함하는 세포 주기 조절자의 발현에 관여함이 밝혀졌으며, 다양한 암에서 PER1과 PER2의 발현 감소가 보고되었다. 따라서, 본 논문에서는 PER1과 PER2의 circadian rhythm에서의 분자적 기능과 종양 발생과 관련된 PER1과 PER2의 하위 표적인자에 대해 살펴보고, 암 치료를 위한 새로운 치료 표적과 암의 예후를 예측하기 위한 분자 지표로써의 PER1과 PER2의 가능성에 대해 서술하고자 한다.

Keywords

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