Cry 1 Regulates the Clock Gene Network and Promotes Proliferation and Migration Via the Akt/P53/P21 Pathway in Human Osteosarcoma Cells

In this study, we investigated the role of Cry1 in regulating proliferation and migration of Hos and U2os human osteosarcoma cells by silencing Cry1 using short hairpin RNA interference. Our data from in vitro and in vivo experiments confirmed that Cry1 knockdown enhanced proliferation and migration of osteosarcoma cells. Then, Cry2, Per1, Per2, Per3, Bmal1 and Clock were found up regulated, while Dec1, Dec2, CK1ε and Npas2 were downregulated at mRNA level. Besides, Akt/P53/P21 signaling was activated after Cry1 silencing and Akt was negatively phosphorylated along with Cry1 expression, while enhanced progression of osteosarcoma cells by Cry1 knockdown was reversed when Akt inhibitor treated. Furthermore, the rescue experiment verified the Akt/P53/P21 was downstream genes of Cry1 to control osteosarcoma progression. Taken together, these findings provide a new insight into how Cry1 regulates clock gene network and promotes proliferation and migration in a Akt dependent manner in human osteosarcoma cells.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research