Period 3, a tumor suppressor in non-small cell lung cancer, is silenced by hypermethylation

Lung cancer is one of the most preventable forms of cancer, which is the second leading cause of cancer-related death. Emerging evidence has suggested a possible link between the endogenous circadian clock and cell growth, and even cancer development. However, the role of important clock gene period 3 (PER3) in lung cancer remains fully understand, especially its regulatory mechanism. In this study, we investigated the biological role of PER3 in non-small cell lung cancer (NSCLC), and also demonstrated the possible mechanism that induces dysfunction of PER3 in lung cancer. QPCR was performed to measure the expression of PER3 in NSCLC tissues and cell lines. Bisulfite genomic sequencing PCR (BSP) and methylation specific PCR (MSP) were used to determine the methylation status of PER3. And a battery of cell biology assays was used to measure the effects of PER3 on cell proliferation, apoptosis, migration and invasion. We found that PER3 was downregulated in NSCLC tissues and cell lines compared with the adjacent or normal cells control. The promoter of PER3 was hypermethylated, which could be restored by demethylation drug 5-Aza. And overexpression of PER3 suppressed NSCLC cell proliferation, induced apoptosis and inhibited the ability of migration and invasion. These findings reveal that PER3 is a tumor suppressor in NSCLC and provide a promising target and a novel strategy to control cancer progression.