Silencing forkhead box M1 promotes apoptosis and autophagy through SIRT7/mTOR/IGF2 pathway in gastric cancer cells.

Forkhead box M1 (FOXM1) was initially identified as an oncogenic transcription factor, and multiple lines of evidence have demonstrated that FOXM1 is abundantly expressed and plays an irreplaceable role in several types of human cancers. Also, evidence has shown the association of FOXM1 with gastric carcinoma metastasis and patients prognosis; however, the potential role and molecular mechanism of FOXM1 in gastric cancer cell apoptosis are still obscure. The current study indicates that FOXM1 is highly expressed in a variety of gastric carcinoma cell lines, such as BGC823, MGC803, AGS, and SGC-7901, compared with the normal gastric mucosal epithelial cell lines CES-1. FOXM1 silence markedly inhibits AGS and SGC-7901 cell survival and proliferation, increases their apoptosis, and modulates apoptosis-related protein expression, including reduced Bcl-2 level and increased Bax and caspase-3 levels. Further study showed that FOXM1 depletion induced cell autophagy through increasing the level of beclin-1 and decreasing the P62 expression. We next corroborated that FOXM1 silence abolished the expression of Sirtuin 7 (SIRT7) and increased the level of insulin-like growth factor 2 (IGF2) and mammalian target of rapamycin (mTOR). Finally, our data documented that the SIRT7/mTOR/IGF2 pathway was involved in the function of FOXM1 in AGS cell growth and apoptosis. In conclusion, these results confirmed that FOXM1 is involved in gastric carcinoma progression via the SIRT7/mTOR/IGF2 pathway.