SIRT7 levels are downregulated and are an independent prognostic factor in gallbladder cancer

Abstract

Abstract Background: Nucleosome-localized sirtuin 7 (SIRT7) has been found to function as an oncogene and tumor suppressor gene in different tumors, respectively. However, the clinical significance of SIRT7 protein in gallbladder cancer (GBC) and the effects of its expression on GBC have not been assessed. Methods: We assessed the levels of SIRT7 protein in tissue microarrays containing 80 GBC patients, and the associations with clinicopathological parameters and overall survival time of GBC patients by immunohistochemical staining. We also constructed GBC cell lines (GBC-SD) with overexpression or interference of SIRT7 by lentiviral infection. The effects of SIRT7 on the proliferation, migration, and invasive ability of GBC-SD cells were then investigated using cell counting kit-8 (CCK-8) assays, wound healing assays, and migration and invasion assays. Additionally, we investigated the effects of SIRT7 on the cell cycle and apoptosis of GBC cells, and the relationship with nuclear factor-κB (NF-κB) pathway. Results: Immunohistochemistry revealed that SIRT7 protein levels were reduced in GBC, and that higher SIRT7 levels were associated with larger tumor volumes, poorer pathological differentiation, later T-staging, later N-staging and later AJCC staging in GBC patients and were an independent prognostic factor in GBC patients. Interfering with SIRT7 significantly inhibited the proliferative viability, scratch healing capacity, migratory capacity, and invasive capacity of GBC-SD cells, whilst overexpression of SIRT7 had the opposite effect. Additionally, interfering with SIRT7 significantly inhibited the cell cycle and increased the apoptosis rate of GBC-SD cells, and inhibited the nuclear translocation of p65 protein. Conclusions: Our study suggests that SIRT7 is an independent prognostic factor for GBC, and that SIRT7 inhibits apoptosis and thus proliferation, migration, and invasion by suppressing NF-κB pathway activity. This suggests that SIRT7 could be a potential target for the diagnosis and treatment of GBC.