Knockdown of FAM3B triggers cell apoptosis through p53-dependent pathway

摘要: FAM3B, also named PANDER, is a cytokine-like protein identified in 2002. Previous studies showed that FAM3B regulates glucose and lipid metabolism through interaction with liver endocrine pancreas. expressed by other tissues but its basic function unclear. In this study, we found was mouse colon, intestine, lung multiple types of cell lines, including murine pancreatic β-cell (Min6), microglia (N9) muscle (C2C12); human colon cancer cells (HCT8, HCT116, HT29), hepatocyte (HL-7702), hepatocellular carcinoma (SMMC-7721) (A549). Inhibition expression RNA interference induced apoptotic death HCT8, A549, N9, C2C12 Min6 decreased viability HL-7702 primary hepatocytes. Further HCT8 knockdown increased the levels membrane-bound Fas Bax, reduced Bcl-2, promoted cleavage caspases-8, -3, -9 PARP, nuclear translocation cleaved PARP. These results suggest silencing activates both extrinsic intrinsic pathways. Mechanistic neutralizing antibody against or Fas-associated domain had no effect on, while caspase inhibitors could significantly reverse apoptosis, suggesting receptor mediated pathway not involved apoptosis. p53 upregulated after knockdown. Silencing almost completely upregulation downregulation -9, death, p53-dependent plays critical roles Studies HCT116 confirmed inhibition apoptosis pathway. Furthermore, level Mdm2 phosphorylation. Taken together, our demonstrated phosphorylation accumulation decreasing expression, which resulted death.