SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1)

Abstract

Sirtuin 1 (SIRT1), class III histone deacetylase, plays an important character in cell proliferation, cell cycle, apoptosis, energy metabolism and DNA repair. In recent years, researchers have attached increasing attention on the role of SIRT1 in tumorigenesis, development and drug resistance. The effect of SIRT1 on breast cancer is still controversial and its exact role remains to be elucidated. In the present study, we investigated the significant role of SIRT1 in breast cancer by exploring the effect of SIRT1 on DNA polymerase delta1 (POLD1), the gene coding for DNA polymerase δ catalytic subunit p125. Immunohistochemistry showed that the protein expression level of SIRT1 was higher in breast cancer tissues relative to adjacent normal tissues. Knockdown of SIRT1 by shRNA decreased the proliferation, migration, and invasion of human breast cancer cell line MCF-7, while the overexpression of SIRT1 promoted the proliferation, migration, and invasion of MCF-7 cells. Clinically, the immunohistochemistry results revealed that the expression of SIRT1 was positively correlated with p125. Further analysis demonstrated that silencing of SIRT1 increased the expression of p53, while the expression level of POLD1/p125 decreased, and the result by overexpressing SIRT1 was opposite. Collectively, these data suggest that SIRT1 is an oncogenic factor in breast cancer cells and can be involved in the progression of breast cancer by inhibiting p53 and activating POLD1. Our finding provides new insights into the mechanisms of breast cancer.