Colorectal cancer cells with stably expressed SIRT3 demonstrate
proliferating retardation by Wnt/β-catenin cascade inactivation
Abstract
Colorectal cancer (CRC) is a typical and lethal digestive system
malignancy. In this study, we investigated the effect of Sirtuin 3
(SIRT3) expression, a fidelity mitochondrial protein, on proliferation
of CRC cells and the related mechanisms. Using UALCAN database and CPTAC
database, we found low expression of SIRT3 in CRC was the unfavorable
factor for survival prognosis. Meanwhile,SIRT3 expression was
correlated with distant metastasis and TNM stage of CRC patients.
Subsequently, we found the proliferating capacities of CRC cells with
stably expressed SIRT3 were decreased dramatically in
vitro and in vivo, with comparison to their counterparts,
respectively. Further western blot (WB), immunoprecipitation (IP) and
TOPflash/FOPflash assay showed the related mechanism of growth
retardation of these cells was highly associated with the degradation of
β-catenin in cytosol, and the localization of β-catenin/α-catenin
complex in nucleus. Taken together, these results revealed the
retardation of CRC cell proliferation by SIRT3 was highly correlated
with the inactivation of Wnt/β-catenin signaling.