High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients.
High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients.
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DOI：
10.1038/srep07481
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发表时间：
2014-12-15
影响因子：
4.6
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Chen X;Sun K;Jiao S;Cai N;Zhao X;Zou H;Xie Y;Wang Z;Zhong M;Wei L
SIRT1是一种依赖于NAD+的III类脱乙酰酶，参与许多重要的生物学过程。先前的研究表明，SIRT1在某些癌症中过表达，并在肿瘤发生中起重要作用。然而，SIRT1与结直肠癌（CRC）之间的关系仍不清楚。我们发现SIRT1在结直肠癌组织中的高表达与结直肠癌患者的不良预后有明显的相关性。同时，SIRT1表达与CD 133（目前表征结直肠癌干细胞（CSC）的通用标志物）共定位。体外研究还显示，SIRT1在结直肠CSC样细胞中过表达。SIRT1缺陷还可降低CRC细胞中CD 133+细胞的比例，减弱集落形成和球体形成的能力，并抑制CRC细胞的体内致瘤性。进一步的研究表明，在CRC细胞中，SIRT1敲低降低了几个干细胞相关基因的表达，包括Oct4，Nanog，Cripto，Tert和Lin28。综上所述，我们的研究结果表明，SIRT1在保持CSC细胞的特性方面起着至关重要的作用。SIRT1是一个潜在的独立的预后因素的CRC患者的肿瘤切除术后的根治性的意图，并将有助于提供一个有前途的新方法，在CRC治疗中的CSC为目标。
SIRT1, a NAD+ dependent class III deacetylase, takes part in many important biological processes. Previous studies show that SIRT1 is overexpressed in some cancers and plays an essential role in tumorigenesis. However, the association between SIRT1 and colorectal cancer (CRC) is still unclear. We found that many CRC specimens had strong SIRT1 expression, which had an obvious correlation with poor prognosis of CRC patients. Meanwhile, SIRT1 expression had a co-localization with CD133, a current universal marker to characterize colorectal cancer stem cells (CSCs). In vitro studies also revealed that SIRT1 was overexpressed in colorectal CSC-like cells. Moreover, SIRT1 deficiency decreased percentage of CD133+ cells, attenuated the abilities of colony and sphere formation, and inhibited tumorigenicity in vivo in CRC cells. Further study demonstrated that the expressions of several stemness-associated genes, including Oct4, Nanog, Cripto, Tert and Lin28, were reduced by SIRT1 knockdown in CRC cells. Taken together, our findings suggest that SIRT1 plays a crucial role in keeping the characteristics of CSCs cells. SIRT1 is a potential independent prognostic factor of CRC patients after tumor resection with curative intent, and will contribute to providing a promising new approach to target at CSCs in CRC treatment.
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影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
DOI：
10.1073/pnas.0409875102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Kuzmichev, A;Margueron, R;Reinberg, D
通讯作者：
Reinberg, D
影响因子：
50.3
作者：
Li L;Wang L;Li L;Wang Z;Ho Y;McDonald T;Holyoake TL;Chen W;Bhatia R
通讯作者：
Bhatia R
影响因子：
23.9
作者：
Han, Myung-Kwan;Song, Eun-Kyung;Broxmeyer, Hal E.
通讯作者：
Broxmeyer, Hal E.
影响因子：
56.9
作者：
Brunet, A;Sweeney, LB;Greenberg, ME
通讯作者：
Greenberg, ME