Circadian clock gene Period2 suppresses human chronic myeloid leukemia cell proliferation

Abstract

Circadian clock genes (CCGs) are reported to serve pivotal roles in regulating the development of certain tumors, including lung cancer and colon cancer . However, their expression patterns and function in chronic myeloid leukemia (CML) remains poorly understood. The present study aimed to investigate the expression and function of circadian clock gene Period2 (Per2) in human CML. Per2 expression levels in neutrophils isolated from patients with CML and healthy donors were measured via reverse transcription-quantitative PCR. Subsequently, through lentivirus transduction, Per2 was stably overexpressed in human CML cell line KCL22 cells, which were injected into nude mice to investigate the in vivo role of Per2 by measuring CML tumor size and weight. Additionally, Per2 expression levels in patients with acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL) were analyzed by re-analyzing microarray data in the Gene Expression Omnibus database. Per2 expression was significantly lower in neutrophils isolated from patients with CML patients compared with healthy donors, and was negatively correlated with the expression level of c-Myc. Similarly, patients with AML or CLL displayed lower Per2 expression levels compared with healthy controls. Per2 overexpression inhibited KCL22 cell proliferation in nude mice and in vitro, and induced cell cycle arrest at the G ₁ phase. By contrast, the results also indicated that KCL22 cell apoptosis was not regulated by Per2. The present study identified Per2 as a potential tumor suppressor in human CML.