Down-regulation of cancer-associated gene CDC73 contributes to cellular senescence
Down-regulation of cancer-associated gene CDC73 contributes to cellular senescence
复制标题
癌症相关基因CDC73的下调导致细胞衰老
DOI：
10.1016/j.bbrc.2018.03.228
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发表时间：
2018-05-23
影响因子：
3.1
通讯作者：
Ni, Ting
中科院分区：
文献类型：
--
作者：
Jia, Qi;Nie, Hongbo;Ni, Ting
基因表达失调是除突变外解释癌症相关表型的另一个重要因素。细胞衰老是预防癌症的一种机制，因此了解衰老过程中基因表达的调控对于抗癌治疗具有重要意义。在这里，我们发现编码细胞分裂周期73并作为肿瘤抑制因子的CDC 73在几种癌症类型中意外上调，但在各种衰老细胞中下调。重要的是，CDC73的缺失可以诱导正常细胞和癌细胞中的衰老相关表型，并增加p21表达。在分子机制方面，选择性多聚腺苷酸化（阿帕）介导的3'非翻译区（3' UTR）延长至少部分解释了衰老细胞中CDC 73表达的降低，因为较长的3' UTR比较短的3' UTR具有更高的RNA降解速率。我们的工作发现，CDC73的转录后下调有助于细胞衰老。(C)2018爱思唯尔公司All rights reserved.
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.