화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.499, No.4, 809-814, 2018
Down-regulation of cancer-associated gene CDC73 contributes to cellular senescence
Dysregulated gene expression is another important contributor in explaining cancer-related phenotypes in addition to mutations. Cellular senescence is a mechanism for the prevention of cancer and thus it is important to understand the regulation of gene expression in senescence due to its potential in anticancer therapy. Here, we found that CDC73, which encodes the cell division cycle 73 and acts as a tumor suppressor, was unexpectedly up-regulated in several cancer types but down-regulated in a variety of senescent cells. Importantly, depletion of CDC73 could induce senescence-associated phenotypes in both normal and cancer cells, with an increase in p21 expression. In terms of molecular mechanism, alternative polyadenylation (APA)-mediated 3' untranslated region (3' UTR) lengthening explained, at least in part, the decreased CDC73 expression in senescent cells because longer 3' UTR had a higher rate of RNA degradation compared to the shorter one. Our work discovered that post-transcriptional down regulation of CDC73 contributed to cellular senescence. (C) 2018 Elsevier Inc. All rights reserved.