SIRT7 is a member of the mammalian sirtuin family and functions as a NAD+-dependent deacylase. Studies in culture cells and human clinical data have implicated the role of SIRT7 in tumorigenesis. However, controversies were raised as to whether SIRT7 is oncogenic or tumor suppressive. Here we show that SIRT7 deficiency led to aneuploidy and aging-phenotypes, including senescence and nucleolin expansion. SIRT7 knockout mice were susceptible to DSS-induced colitis and alcohol-derived DNA damage, in advance led to intestinal epithelial barrier disruption. Devoid of SIRT7 aggravated the susceptibility of colorectal cancer incidence in APCMin/+ mouse model with further dysregulated Wnt signaling. Our findings indicated a tumor suppressive role of SIRT7 in vivo, novel strategies design for activating SIRT7 in treating colon cancer may be reappraised. SOURCE: Xiyang Liu (liuxy@sibs.ac.cn) - Laboratory of Cancer Biology and Genetics Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences

Pluto Bioinformatics

GSE138289: SIRT7 safeguards genome stability and suppresses colorectal tumorigenesis