Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway
The present research shows the clock gene Per2 is expressed at ‘abnormal’ amounts in a number of tumors and plays a substantial tumor suppressor role. However, the biological functions and mechanism of Per2 in OSCC (OSCC: dental squamous cell carcinoma) remain unclear. Within this study, OSCC cells with stable overexpression or silencing of Per2 were created explore their biological functions and mechanism in vivo as well as in vitro. We learned that the expression of Per2 decreases in OSCC cells. Overexpression of Per2 promoted autophagy and apoptosis in OSCC cells and inhibited proliferation. The alternative outcome was acquired in Per2-silenced OSCC cells. In Per2-overexpressing OSCC cells, the expression amounts of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were considerably reduced and also the LC3B II/I ratio was considerably elevated. In comparison, in Per2-silenced OSCC cells, the expression amounts of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were considerably enhanced and also the LC3B II/I ratio was considerably reduced. Once the AKT activator SC79 was put into Per2-overexpressing OSCC cells, the elevated autophagy, apoptosis and decreased proliferation were considerably saved. In addition, when autophinib, an autophagy inhibitor, was put into Per2-overexpressing OSCC cells, the decreased proliferation and elevated apoptosis were considerably restored. An in vivo tumorigenesis assay also confirmed that overexpression of Per2 suppresses the development of OSCC. To conclude, our research results show Per2 suppresses OSCC progression by motivating autophagy, in addition to inhibiting cell proliferation and promoting apoptosis, that have been mediated by autophagy, inside a PI3K/AKT/mTOR path-dependent manner. Per2 may potentially be utilized for an invaluable therapeutic marker for OSCC.