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Abnormal expression of the clock gene PER1 is highly correlated with carcinogenesis and the development of malignant tumors. Here, we designed short hairpin RNAs (shRNAs) to effectively knock down PER1 in SCC15 human oral squamous cell carcinoma cells. shRNA-mediated PER1 knockdown promoted SCC15 cell growth, proliferation, apoptosis resistance, migration and invasion in vitro. PER1 knockdown also increased the cells' expression of KI-67, MDM2, BCL-2, MMP2 and MMP9 mRNA, and decreased expression of C-MYC, p53, BAX and TIMP-2. In BALB/c nu/nu nude mice subcutaneously injected with SCC15 cells, PER1 knockdown in the cells enhanced tumor development, leading to increased tumor weights and volumes. These results suggest that PER1 is an important tumor suppressor gene and may be a useful molecular target for the treatment of cancer.

Objective: To investigate the effect and regulatory mechanism of clock gene Per1 on the proliferation,apoptosis,migration,and invasion of human oral squamous carcinoma SCC15 cells., Methods: RNA interference was used to knock down Per1 gene in human oral squamous cell carcinoma SCC15 cell line. Changes of cell proliferation and apoptosis were analyzed by flow cytometry. Transwell assay was carried out to assess cell migration and invasion. Real-time polymerase chain reaction was used to detect the mRNA expressions of Ki-67, murine double minute 2 (MDM2), c-Myc, p53, Bax, Bcl-2, metalloproteinase (MMP)2, MMP9, and vascular endothelial growth factor (VEGF)., Results: shRNA-mediated knockdown of Per1 promoted the proliferation, migration and invasion capacity, and inhibited cell apoptosis capacity of SCC15 cells (all P<0.05). Additionally, Per1 knockdown also increased the mRNA expressions of Ki-67, MDM2, Bcl-2, MMP2, and MMP9 and decreased the mRNA expressions of c-Myc, p53, and Bax (all P<0.05); however, the VEGF mRNA expression did not differ significantly after Per1 knockdown (P>0.05)., Conclusions: Clock gene Perl can regulate important tumor-related genes downstream such as Ki-67, MDM2, c-Myc, p53, Bax, Bcl-2, MMP2, and MMP9, and the aberrant expression of Per1 can affect tumor cell proliferation,apoptosis,migration and invasion. An in-depth study of Per1 may further clarify the mechanism of tumorigenesis and tumor development and thus provides new effective molecular targets for cancer treatment.