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Abstract: PERIOD (PER) proteins are transcriptional regulators that are involved in circadian rhythms, sleep homeostasis, cell proliferation and tumour progression. We previously showed that the expression of PER1 was related to the regulation of apoptosis in human pancreatic cancer and hepatocellular carcinoma cells. However, the significance of PER in oral cancer has not been reported, and the detailed molecular mechanisms by which anti-tumour drug induces apoptosis in gingival cancer cells are not well understood. We examined whether PER1 and PER3 are involved in the regulation of apoptosis in human gingival cancer CA9-22 cells. The expression of PER1 and PER3 was upregulated and downregulated, respectively, by cis-diamminedichloroplatinum (II) (cisplatin: CDDP) treatment in CA9-22 cells, whereas CDDP treatment had little effects on the expression of PER1 and PER3 in human gingival fibroblasts (HGF-1). We found that short interference RNA (siRNA)-mediated knockdown of PER1 enhanced apoptosis of CA9-22 cells, and that PER1 regulated the amount of Bim, an apoptosis-related molecule. On the other hand, PER3 knockdown had an inhibitory effect on the apoptosis of CA9-22 cells induced by CDDP treatment. These results suggest that the alternation of expression of PER1 and PER3 was related to the apoptosis of CA9-22 cells. Furthermore, PER1 was intensely stained in the gingival cancer tissues, whereas PER3 was significantly stained in the non-tumour tissues by immunohistochemistry. These findings suggest that PER1 and PER3 have anti-apoptotic and pro-apoptotic effects in human gingival cancer CA9-22 cells, respectively. The balance of PER1 and PER3 may modulate apoptotic reactions in gingival cancer cells. [Copyright &y& Elsevier]

Introduction: Prostate cancer (PCa) is one of the most common cancers affecting men globally. Although PER3 has been suggested as a risk factor for cancer development, there are few reports elucidating the relationship between PER3 and PCa. We investigated the association between PER3 polymorphisms (rs2640908 and VNTR) and susceptibility to PCa in the Japanese population., Methods: Eighty three patients with PCa and 122 controls participated in this study. We analyzed rs2640908 and VNTR polymorphisms by using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP)., Results: Compared to the C/C genotype with the rs2640908 polymorphism, the T/T (OR: 0.35, 95% CI: 0.15-0.81, P = 0.02) and C/T + T/T (OR: 0.46, 95% CI: 0.24-0.88, P = 0.02) genotypes had a significantly lower risk of PCa. TT (OR: 0.29, 95% CI: 0.10-0.77, P = 0.02) and CT + TT (OR: 0.47, 95% CI: 0.23-0.97, P = 0.04) also had significant protection against PCa in the smoker group. Significantly, we observed an association between smoking and rs2640908 polymorphism in this study. However, no association between the VNTR polymorphisms and PCa was detected., Conclusions: Our results suggest that PER3 rs2640908 polymorphisms influence an individual's susceptibility to PCa., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (©2021 Pacini Editore SRL, Pisa, Italy.)